19 results on '"linagliptin"'
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2. A Randomized, Double-Blind, Parallel-Group Phase III Trial Investigating the Glycemic Efficacy and Safety Profile of Fixed-Dose Combination Dapagliflozin and Linagliptin Over Linagliptin Monotherapy in Patients with Inadequately Controlled Type 2 Diabetes with Metformin
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Jain, Aditi, Vispute, Abhay, Dange, Amol, Naskar, Arindam, Mondal, Asish, Vivekanand, B., Sharma, Balram, Varade, Deepak, Shukla, Dhaiwat, Bhatia, Girish, Chaudhari, Harshal, Ram Babu, K., Gavali, Onkar, Sorate, Sanket, Bhanushali, Shaishav, Kothari, Vaibhav, Khandelwal, Vipul, Sharma, Akhilesh, Pawar, Roshan, and Mayabhate, Mayur
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CLINICAL trials , *TYPE 2 diabetes , *LINAGLIPTIN , *DAPAGLIFLOZIN , *METFORMIN - Abstract
Introduction: The aim of the study was to evaluate the efficacy and safety of fixed-dose combination (FDC) of dapagliflozin (10 mg) and linagliptin (5 mg) in comparison to linagliptin 5 mg (Trajenta) in patients with insufficiently controlled type 2 diabetes mellitus (T2DM) on metformin monotherapy. Methods: The double-blind, randomized, multicentric, parallel-group phase III trial screened 287 adult patients with T2DM (age 18–65 years) from 16 sites across India. The recruited subjects were undergoing metformin monotherapy ≥ 1000 mg/day for at least 28 days. Patients with HbA1c of 7.5–10.5% (58–91 mmol/l) (n = 232) after 2 weeks of run-in period with linagliptin monotherapy and placebo dapagliflozin/linagliptin on metformin monotherapy were randomized (1:1) in parallel to once daily dapagliflozin/linagliptin 10/5 mg or linagliptin 5 mg for 16 weeks. Patients were stratified on the basis of HbA1c (≤ 9.0% and > 9.0%; ≤ 75 mmol/l and > 75 mmol/l)). A total of 225 subjects completed 16 weeks of treatment, 115 patients in the test group and 110 patients in the reference group. Results: Dapagliflozin/linagliptin (p = 0.0003) exhibited a greater change in HbA1c from baseline than linagliptin (p < 0.0001) in 16 weeks (mean reduction, − 1.28% vs − 0.83%). Test group showed a significant decrease in fasting plasma glucose (FPG), postprandial plasma glucose (PPG) and body weight compared to the reference group. The FDC was well tolerated with adverse events being more frequent in the reference group. No serious adverse events (SAEs) were reported in the study. Conclusion: Dapagliflozin/linagliptin combination is a novel dipeptidyl peptidase 4 (DPP4)/sodium-glucose co-transporter 2 (SGLT2) inhibitor FDC approved in India for patients with T2DM. Potential limitations of this study are a small dose of dapagliflozin (10 mg) in the FDC, a short study duration (30 weeks) and a high minimum threshold for HbA1c (≤ 7.5%; ≤ 53 mmol/l). Results indicate the FDC to be a superior therapeutic option over linagliptin for patients with T2DM on metformin monotherapy. Trial Registration: CTRI/2022/08/044563; 01/08/2022. [ABSTRACT FROM AUTHOR]
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- 2024
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3. Effects of the Once-Weekly DPP4 Inhibitor Omarigliptin on Glycemic Control in Patients with Type 2 Diabetes Mellitus on Maintenance Hemodialysis: A 24-Week Open-Label, Multicenter Randomized Controlled Study.
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Yoshizawa, Yuta, Hosojima, Michihiro, Kabasawa, Hideyuki, Tanabe, Naohito, Ugamura, Daisuke, Koda, Yutaka, Shimada, Hisaki, Takasawa, Tetsuya, Ito, Takahito, Kitamura, Tadahiro, Kobayashi, Masaki, Suzuki, Yoshiki, Narita, Ichiei, and Saito, Akihiko
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TYPE 2 diabetes , *GLYCEMIC control , *GLYCOSYLATED hemoglobin , *CLINICAL trial registries , *CD26 antigen , *SODIUM-glucose cotransporters - Abstract
Introduction: Dipeptidyl peptidase 4 (DPP4) inhibitors are widely used in patients with type 2 diabetes mellitus (T2DM) on maintenance hemodialysis (HD), but the efficacy of the once-weekly DPP4 inhibitor omarigliptin is not known. Methods: This prospective, randomized, open-label, parallel-group, non-inferiority/superiority, once-daily DPP4 inhibitor linagliptin-controlled, multicenter study examined glycemic control and safety of omarigliptin (UMIN000024284). Sample size was calculated to confirm non-inferiority in terms of changes in glycated hemoglobin (HbA1c). We enrolled 33 patients with T2DM on maintenance HD who had been treated with linagliptin for at least 3 months. The patients were randomized to receive omarigliptin (12.5 mg/week; n = 16) or linagliptin (5 mg/day; n = 17). Primary endpoints were changes in HbA1c and glycoalbumin (GA) over 24 weeks. Results: Differences in the mean change in primary endpoint values between the omarigliptin and linagliptin groups were − 0.61% [− 1.14, − 0.09] for HbA1c, with a two-tailed upper 95% limit (i.e., one-tailed 97.5% upper limit) of 0.25%, below the non-inferiority limit, and − 1.67% [− 4.23, + 0.88] for GA, with a two-tailed upper 95% limit of 0.75%, above the non-inferiority limit. At 24 weeks, the omarigliptin group showed significantly greater reduction in HbA1c than the linagliptin group (− 0.2% ± 0.6% vs. 0.4% ± 0.8%, two-tailed p = 0.024) and significantly greater reduction in blood glucose after a single HD session (− 18.4 ± 31.4 mg/dL vs. 25.2 ± 59.5 mg/dL, respectively, two-tailed p = 0.019). No subjects in the omarigliptin group developed hypoglycemia. Conclusions: Our data showed that omarigliptin was non-inferior to linagliptin in glycemic control. Omarigliptin is feasible for glycemic control in patients with T2DM on maintenance HD. Clinical Trials Registration: UMIN000024284. [ABSTRACT FROM AUTHOR]
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- 2021
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4. Cost-Effectiveness Analysis of Linagliptin in Japan Based on Results from the Asian Subpopulation in the CARMELINA® Trial.
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Watada, Hirotaka, Sakamaki, Hiroyuki, Yabe, Daisuke, Yamamoto, Fumiko, Murata, Tatsunori, Hanada, Keigo, Hirase, Tetsuaki, and Okamura, Tomoo
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COST effectiveness , *QUALITY-adjusted life years , *MEDICAL history taking , *HISTORY of accounting , *TYPE 2 diabetes , *LINAGLIPTIN - Abstract
Introduction: We evaluated the cost-effectiveness of linagliptin in Japan by estimating the lifetime outcome based on clinical event rates from the Asian subpopulation of the CARMELINA trial. In CARMELINA, linagliptin added to standard of care (SoC) versus SoC demonstrated noninferiority with regard to risk of composite cardiovascular (CV) outcome in patients with type 2 diabetes at high risk of CV and kidney events. Issues resulting from conducting a cost-effectiveness analysis using data from a clinical noninferiority study were also investigated. Methods: A microsimulation model was used to evaluate linagliptin/SoC versus SoC in terms of direct costs and quality-adjusted life years (QALYs) from a Japanese public healthcare payer's perspective. Cost data were obtained from recent Japanese publications. The time horizon was defined as lifetime, and the discount rate for costs and effectiveness was 2% per year. One-way and probabilistic sensitivity analyses were performed. Results: In the base case analysis, and taking medical history into account, the incremental effectiveness of linagliptin/SoC versus SoC was 1.34 QALYs, and the incremental cost for linagliptin was − 545,319 yen. In the one-way sensitivity analysis, the parameter which most affected the results was the hazard ratio for renal failure of linagliptin/SoC compared with SoC. The probabilistic sensitivity analysis showed that the probability of reduced costs and increased effectiveness (dominant) was 48%. Assuming an incremental cost-effectiveness ratio (ICER) threshold of 5 million yen, the probability that the ICER was below the threshold was 89% for linagliptin/SoC compared with SoC. Conclusions: This evaluation, using Asian subpopulation data from the CARMELINA trial, suggested that the cost-effectiveness of linagliptin for a lifetime outcome was favourable in Japan. However, the results must be interpreted cautiously because of the noninferiority trial data source, which might cause ICER variations for each parameter. [ABSTRACT FROM AUTHOR]
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- 2020
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5. Real-World Glycemic Lowering Effectiveness of Linagliptin Among Adults with Type 2 Diabetes by Age, Renal Function, and Race.
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Hoogwerf, Byron J., MacKenzie, Michele, Sealls, Whitney, Cordova, Jeanine, and Gandhi, Pranav
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TYPE 2 diabetes , *OLDER people , *GLYCOSYLATED hemoglobin , *GLOMERULAR filtration rate , *ADULTS , *LINAGLIPTIN - Abstract
Introduction: To assess real-world effectiveness of linagliptin in persons with type 2 diabetes mellitus (T2DM) across a range of ages and renal function. Effectiveness was assessed in different races, with a focus on African Americans (AA). Methods: This was a non-interventional retrospective cohort study using data in the Optum clinical database from adults with T2DM initiating linagliptin. Date of the first linagliptin prescription was the index date. Outcomes included change in glycated hemoglobin (HbA1c) and the percentage of persons achieving an HbA1c < 7% (53 mmol/mol) during the 60–180 days following linagliptin initiation. Analyses of age by renal function were conducted. Multivariate regression analysis was performed to assess change in HbA1c, controlling for an a priori list of covariates. Results: Overall, 11,001 persons were included. Mean pre-index HbA1c value was 8.2% (66 mmol/mol), with higher levels in younger versus older persons and AAs versus other race groups. Persons initiating linagliptin had an average HbA1c reduction of 0.51% (5.6 mmol/mol). Without adjusting for age, renal function, race, and pre-index HbA1c, greater reductions in HbA1c were observed in younger versus older persons, persons with higher versus lower estimated glomerular filtration rate (eGFR), and AAs versus white or Asians. After multivariate analysis, variables significantly associated with a greater HbA1c reduction included higher pre-index HbA1c and older age. Conclusions: These results support the HbA1c-lowering effectiveness of linagliptin across age, race, and renal function categories among a large real-world population of adults with T2DM. [ABSTRACT FROM AUTHOR]
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- 2020
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6. Early Combination Therapy with Linagliptin and Metformin in People with Type 2 Diabetes Improves Glycemic Control to HbA1c ≤ 6.5% without Increasing Hypoglycemia: Pooled Analysis of Two Randomized Clinical Trials.
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Lv, Qian, Shen, Jie, Miao, Lin, Ye, Binqi, Schepers, Cornelia, Plat, Arian, and Shi, Yongquan
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TYPE 2 diabetes , *GLYCEMIC control , *METFORMIN , *HYPOGLYCEMIA , *GLYCOSYLATED hemoglobin , *LINAGLIPTIN - Abstract
Introduction: Clinical guidelines suggest a glycated hemoglobin A1c (HbA1c) target of ≤ 6.5% for type 2 diabetes patients with short duration of disease, few comorbidities and/or long life expectancy—provided this goal can be achieved safely. We explored whether initial combination treatment with the dipeptidyl peptidase-4 inhibitor linagliptin and metformin could provide better glycemic control (HbA1c ≤ 6.5%) than metformin alone without increasing hypoglycemia. Methods: We pooled and analyzed individual patient data from two randomized clinical trials of early combination therapy with linagliptin and metformin versus metformin monotherapy. The primary outcome in both trials was the change in HbA1c from baseline to week 24. We evaluated the percentage of patients who achieved HbA1c ≤ 6.5% at week 24 and the incidence of adverse events. Results: Most (> 70%) of the 1160 patients analyzed were treatment naive, and more than half had had diabetes for ≤ 1 year; mean baseline HbA1c was approximately 8.7%. Combination therapy with linagliptin and metformin resulted in more patients achieving HbA1c ≤ 6.5% than metformin alone, both for a metformin dose of 500 mg (40.1 vs. 22.9%, respectively, odds ratio [OR] 2.84, 95% confidence interval [CI] 1.87–4.32) and 1000 mg (49.5 vs. 35.4%, respectively, OR 2.28, 95% CI 1.54–3.40). Hypoglycemia occurred in < 3% of patients, with a comparable incidence between treatment groups. Other adverse events were also balanced between groups. Conclusion: Early combination treatment with linagliptin and metformin can improve the chances of achieving tight glycemic control (HbA1c ≤ 6.5%) without increasing the risk of hypoglycemia or other adverse events. Trial Registration: ClinicalTrials.gov, NCT00798161 and NCT01708902. [ABSTRACT FROM AUTHOR]
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- 2020
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7. Long-Term Safety and Effectiveness of Linagliptin in Japanese Patients with Type 2 Diabetes and Renal Dysfunction: a Post-Marketing Surveillance Study.
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Yamamoto, Fumiko, Ikeda, Rie, Ochiai, Kaori, Hirase, Tetsuaki, Hayashi, Naoyuki, and Okamura, Tomoo
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TYPE 2 diabetes , *DRUG side effects , *GLYCOSYLATED hemoglobin , *GLOMERULAR filtration rate , *GLYCEMIC control , *LINAGLIPTIN - Abstract
Introduction: International clinical trials have shown that linagliptin significantly improves glycemic control and can be used at a single dose regardless of renal function in patients with type 2 diabetes (T2D). However, to date, no studies have evaluated the use of linagliptin in Japanese patients with T2D by renal function in routine clinical care. Methods: This was a subgroup analysis of data from a prospective observational post-marketing surveillance (PMS) study of linagliptin conducted in Japan that evaluated the safety and effectiveness of linagliptin in routine clinical care for 3 years in Japanese patients with T2D. The subgroup analysis examined the patient population of this PMS study according to renal function using estimated glomerular filtration rate (eGFR) data. The incidence of linagliptin-related adverse events (adverse drug reactions [ADRs]) was the primary endpoint, and the change in glycated hemoglobin (HbA1c) from baseline to last observation was the secondary endpoint. Results: Of the 2235 patients included in the safety analysis, eGFR was ≥ 90 mL/min/1.73 m2 (defined as group G1) in 16.9% (n = 377), ≥ 60 to < 90 mL/min/1.73 m2 (group G2) in 44.5% (n = 995), ≥ 30 to < 60 mL/min/1.73 m2 (group G3) in 21.7% (n = 486), ≥ 15 to < 30 mL/min/1.73 m2 (group G4) in 2.6% (n = 58) and < 15 mL/min/1.73 m2 (group G5) in 1.7% (n = 37). No eGFR data were available for 12.6% (n = 282) of patients. In these GFR groups, the incidence of ADRs with linagliptin was 6.9% in group G1, 11.1% in group G2, 13.8% in group G3, 15.5% in group G4 and 16.2% in group G5; the change in HbA1c from baseline to the last observation was − 1.11, − 0.64, − 0.35, − 0.46 and − 0.54% in the respective subgroups. Conclusions: Long-term linagliptin use showed sustained improvements in glycemic control with no new safety concerns regardless of renal function. Trial Registration: ClinicalTrials.gov (NCT01650259). Funding: This study was funded by Nippon Boehringer Ingelheim Co., Ltd. and Eli Lilly Japan K.K. [ABSTRACT FROM AUTHOR]
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- 2020
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8. Long-Term Safety and Effectiveness of Linagliptin in Japanese Patients with Type 2 Diabetes Mellitus: A 3-Year Post-Marketing Surveillance Study.
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Yamamoto, Fumiko, Unno, Yuriko, Okamura, Tomoo, Ikeda, Rie, Ochiai, Kaori, and Hayashi, Naoyuki
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TYPE 2 diabetes , *GLYCOSYLATED hemoglobin , *DRUG side effects , *LINAGLIPTIN - Abstract
Introduction: Clinical trials of linagliptin in Japanese patients conducted to date have had limited observational periods; therefore, there is a need for additional longer-term real-world data. The aim of this study was to investigate the long-term safety and effectiveness of linagliptin in routine clinical practice. Methods: This was a prospective, observational, post-marketing surveillance study conducted over 156 weeks in patients with type 2 diabetes mellitus who started linagliptin monotherapy. The primary endpoint was the incidence of adverse drug reactions (ADRs). The secondary endpoint was the change in glycated hemoglobin (HbA1c) from baseline to last available observation. Other effectiveness endpoints included the change in HbA1c and change in fasting plasma glucose (FPG) from baseline to week 26 and over the course of the treatment period. Results: Overall, 2235 and 2054 patients were included in the safety and effectiveness analysis sets, respectively. Patients were mostly male (58.4%), and the mean age was 66.7 years. The incidence of ADRs was 10.7% (n = 240). The most frequent ADRs according to MedDRA preferred terms were diabetes mellitus (n = 35 patients, 1.6%), constipation (n = 21, 0.9%), diabetes mellitus inadequate control (n = 13, 0.6%) and hypertension (n = 13, 0.6%). The mean change in HbA1c from baseline to last observation was − 0.67% [standard deviation (SD) 1.27%, 95% confidence interval − 0.72, − 0.61]. At week 26, HbA1c and FPG showed mean ± SD changes from baseline of – 0.73 ± 1.20% and − 21.02 ± 44.33 mg/dL, respectively, that were sustained until week 156. Conclusions: In Japanese patients with type 2 diabetes mellitus, linagliptin produced sustained reductions in HbA1c and had a safety profile consistent with the established safety profile of linagliptin. Trial Registration: ClinicalTrials.gov (NCT01650259). [ABSTRACT FROM AUTHOR]
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- 2020
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9. The Effect of Linagliptin versus Metformin Treatment-Related Quality of Life in Patients with Type 2 Diabetes Mellitus.
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Mita, Tomoya, Hiyoshi, Toru, Yoshii, Hidenori, Chimori, Hiroko, Ikeda, Kazuo, Shimizu, Miho, Kojima, Yuichi, Yamamto, Hareaki, Yasuda, Daijiro, Sato, Junko, and Watada, Hirotaka
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TYPE 2 diabetes , *DIET therapy , *EXERCISE therapy , *DIABETES , *METFORMIN , *LINAGLIPTIN - Abstract
Introduction: There have been no studies directly comparing the effect of dipeptidyl peptidase-4 inhibitors with that of metformin on treatment-related quality of life (QOL) when used as first-line therapy in patients with type 2 diabetes mellitus (T2DM).Methods: This study is a prospective, randomized, open-label, multicenter, parallel-group, comparative study. Forty-four participants who failed to achieve target glycemic control with diet and exercise therapy were randomly allocated to receive linagliptin or metformin therapy. We compared treatment-related QOL among the two groups using the Oral Hypoglycemic Agent Questionnaire, version 2 (OHA-Q version 2) and the self-administered Diabetes Therapy-Related QOL (DTR-QOL) questionnaire.Results: After randomization, 21 patients in the linagliptin group and 22 patients in the metformin treatment group were included in the full analysis set. Biochemical parameters, incidence of adverse effects, and rate of adherence to medication were comparable between the two groups. Over the 24-week treatment period, no significant differences in overall OHA-Q scores between the groups were observed, although the subscale 1 (treatment convenience) score was significantly higher in the linagliptin group than in the metformin group. The overall DTR-QOL score did not differ between the two groups; however, the DTR-QOL scores significantly improved after 24 weeks of linagliptin treatment, but not after metformin treatment.Conclusion: We did not find significantly better treatment-related QOL with linagliptin among Japanese patients with T2DM. In terms of treatment convenience, our data showed that linagliptin was superior to metformin.Funding: This study was financially supported by Nippon Boehringer Ingelheim Co., Ltd. and Eli Lilly and Company. The journal's article processing fees were covered by a research fund from Juntendo University.Clinical Trial Registration: UMIN000022953. [ABSTRACT FROM AUTHOR]
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- 2019
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10. Safety and Efficacy of DPP4 Inhibitor and Basal Insulin in Type 2 Diabetes: An Updated Review and Challenging Clinical Scenarios.
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Gomez-Peralta, Fernando, Abreu, Cristina, Gomez-Rodriguez, Sara, Barranco, Rafael J., and Umpierrez, Guillermo E.
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INSULIN , *CD26 antigen , *GLYCEMIC control , *TYPE 2 diabetes , *CLINICAL trials - Abstract
The safety and efficacy of dipeptidyl peptidase-4 (DPP4) inhibitors as monotherapy or in combination with other oral antidiabetic agents or basal insulin are well established. DPP4 inhibitors stimulate glucose-dependent insulin secretion and inhibit glucagon production. As monotherapy, they reduce the hemoglobin A1c level by about 0.6-0.8%. The addition of a DPP4 inhibitor to basal insulin is an attractive option, because they lower both postprandial and fasting plasma glucose concentrations without increasing the risk of hypoglycemia or weight gain. The present review summarizes the extensive evidence on the combination therapy of DPP4 inhibitors and insulin-based regimens in patients with type 2 diabetes. We focus our discussion on challenging clinical scenarios including patients with chronic renal impairment, elderly persons and hospitalized patients. The evidence indicates that these drugs are highly effective and safe in the elderly and in the presence of mild, moderate and severe renal failure improving glycemic control with low risk of hypoglycemia. In addition, several randomized-controlled trials have shown that the use of DPP4 inhibitors in combination with basal insulin represents an alternative to the basal-bolus insulin regimen in hospitalized patients with type 2 diabetes. [ABSTRACT FROM AUTHOR]
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- 2018
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11. Study Protocol for the Initial Choice of DPP-4 Inhibitor in Japanese Patients with Type 2 diabetes Mellitus: Effect of Linagliptin on QOL (INTEL-QOL) Trial.
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Mita, Tomoya, Hiyoshi, Toru, Yoshii, Hidenori, Chimori, Hiroko, Ikeda, Kazuo, Sato, Junko, and Watada, Hirotaka
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QUALITY of life , *CD26 antigen , *GLYCEMIC control , *TYPE 2 diabetes , *BLOOD sugar monitoring - Abstract
Introduction: Consideration of treatment-related quality of life (QOL) is important in diabetes management. However, no studies have compared the influence of dipeptidyl peptidase-4 inhibitors versus metformin on treatment-related QOL when used as first-line therapy in patients with type 2 diabetes mellitus.Methods: This study is a prospective, randomized, open-label, multicenter, parallel-group, comparative study. Between June 2016 and December 2017, 44 participants who failed to achieve glycemic control despite diet and exercise therapy were recruited at 14 clinics and randomly allocated to linagliptin or metformin therapy. Treatment-related QOL was assessed with the Oral Hypoglycemic Agent Questionnaire, version 2 (OHA-Q ver. 2) and the self-administered Diabetes Therapy-Related QOL (DTR-QOL) questionnaire. The primary study outcome is the difference in total OHA-Q ver. 2 score between the two treatment groups at the end of the study. The secondary outcomes include differences in the scores for each OHA-Q ver. 2 subscale between the two treatment groups at the end of the study, change in total DTR-QOL score and for each domain from baseline to the end of treatment, changes in glycemic control, and adverse events.Planned outcome: The present study is designed to assess the effects of linagliptin on the treatment-related QOL. Results will be available in the near future. Study findings are expected to provide useful information on how to maintain or improve QOL in patients with type 2 diabetes mellitus treated with insulin.Funding: Nippon Boehringer Ingelheim Co., Ltd. and Eli Lilly and Company.Clinical trial registration: UMIN000022953. [ABSTRACT FROM AUTHOR]
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- 2018
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12. Effects of the Once-Weekly DPP4 Inhibitor Omarigliptin on Glycemic Control in Patients with Type 2 Diabetes Mellitus on Maintenance Hemodialysis: A 24-Week Open-Label, Multicenter Randomized Controlled Study
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Naohito Tanabe, Michihiro Hosojima, Tetsuya Takasawa, Ichiei Narita, Yuta Yoshizawa, Takahito Ito, Daisuke Ugamura, Hisaki Shimada, Yoshiki Suzuki, Yutaka Koda, Tadahiro Kitamura, Hideyuki Kabasawa, Masaki Kobayashi, and Akihiko Saito
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medicine.medical_specialty ,Endocrinology, Diabetes and Metabolism ,medicine.medical_treatment ,030209 endocrinology & metabolism ,Linagliptin ,030204 cardiovascular system & hematology ,Hypoglycemia ,Gastroenterology ,law.invention ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Randomized controlled trial ,law ,Internal medicine ,Diabetes mellitus ,Internal Medicine ,medicine ,Clinical endpoint ,Once-weekly dipeptidase 4 inhibitor ,Glycemic ,Original Research ,Type 2 diabetes mellitus ,business.industry ,Omarigliptin ,medicine.disease ,chemistry ,Hemodialysis ,Glycated hemoglobin ,business ,medicine.drug - Abstract
Introduction Dipeptidyl peptidase 4 (DPP4) inhibitors are widely used in patients with type 2 diabetes mellitus (T2DM) on maintenance hemodialysis (HD), but the efficacy of the once-weekly DPP4 inhibitor omarigliptin is not known. Methods This prospective, randomized, open-label, parallel-group, non-inferiority/superiority, once-daily DPP4 inhibitor linagliptin-controlled, multicenter study examined glycemic control and safety of omarigliptin (UMIN000024284). Sample size was calculated to confirm non-inferiority in terms of changes in glycated hemoglobin (HbA1c). We enrolled 33 patients with T2DM on maintenance HD who had been treated with linagliptin for at least 3 months. The patients were randomized to receive omarigliptin (12.5 mg/week; n = 16) or linagliptin (5 mg/day; n = 17). Primary endpoints were changes in HbA1c and glycoalbumin (GA) over 24 weeks. Results Differences in the mean change in primary endpoint values between the omarigliptin and linagliptin groups were − 0.61% [− 1.14, − 0.09] for HbA1c, with a two-tailed upper 95% limit (i.e., one-tailed 97.5% upper limit) of 0.25%, below the non-inferiority limit, and − 1.67% [− 4.23, + 0.88] for GA, with a two-tailed upper 95% limit of 0.75%, above the non-inferiority limit. At 24 weeks, the omarigliptin group showed significantly greater reduction in HbA1c than the linagliptin group (− 0.2% ± 0.6% vs. 0.4% ± 0.8%, two-tailed p = 0.024) and significantly greater reduction in blood glucose after a single HD session (− 18.4 ± 31.4 mg/dL vs. 25.2 ± 59.5 mg/dL, respectively, two-tailed p = 0.019). No subjects in the omarigliptin group developed hypoglycemia. Conclusions Our data showed that omarigliptin was non-inferior to linagliptin in glycemic control. Omarigliptin is feasible for glycemic control in patients with T2DM on maintenance HD. Clinical Trials Registration UMIN000024284. Supplementary Information The online version contains supplementary material available at 10.1007/s13300-020-00991-y.
- Published
- 2021
13. Cost-Effectiveness Analysis of Linagliptin in Japan Based on Results from the Asian Subpopulation in the CARMELINA® Trial
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Keigo Hanada, Tetsuaki Hirase, Hirotaka Watada, Tatsunori Murata, Daisuke Yabe, Tomoo Okamura, Fumiko Yamamoto, and Hiroyuki Sakamaki
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Standard of care ,CARMELINA trial ,Endocrinology, Diabetes and Metabolism ,Linagliptin ,030209 endocrinology & metabolism ,MACE ,Cardiorenal events ,030204 cardiovascular system & hematology ,Public healthcare ,DPP4 inhibitor ,QALY ,03 medical and health sciences ,Indirect costs ,0302 clinical medicine ,Japan ,Microsimulation model ,Statistics ,Internal Medicine ,Medicine ,Sensitivity analyses ,health care economics and organizations ,Original Research ,ICER ,business.industry ,Cost-effectiveness analysis ,Diabetes ,Hazard ratio ,business ,medicine.drug - Abstract
Introduction We evaluated the cost-effectiveness of linagliptin in Japan by estimating the lifetime outcome based on clinical event rates from the Asian subpopulation of the CARMELINA trial. In CARMELINA, linagliptin added to standard of care (SoC) versus SoC demonstrated noninferiority with regard to risk of composite cardiovascular (CV) outcome in patients with type 2 diabetes at high risk of CV and kidney events. Issues resulting from conducting a cost-effectiveness analysis using data from a clinical noninferiority study were also investigated. Methods A microsimulation model was used to evaluate linagliptin/SoC versus SoC in terms of direct costs and quality-adjusted life years (QALYs) from a Japanese public healthcare payer’s perspective. Cost data were obtained from recent Japanese publications. The time horizon was defined as lifetime, and the discount rate for costs and effectiveness was 2% per year. One-way and probabilistic sensitivity analyses were performed. Results In the base case analysis, and taking medical history into account, the incremental effectiveness of linagliptin/SoC versus SoC was 1.34 QALYs, and the incremental cost for linagliptin was − 545,319 yen. In the one-way sensitivity analysis, the parameter which most affected the results was the hazard ratio for renal failure of linagliptin/SoC compared with SoC. The probabilistic sensitivity analysis showed that the probability of reduced costs and increased effectiveness (dominant) was 48%. Assuming an incremental cost-effectiveness ratio (ICER) threshold of 5 million yen, the probability that the ICER was below the threshold was 89% for linagliptin/SoC compared with SoC. Conclusions This evaluation, using Asian subpopulation data from the CARMELINA trial, suggested that the cost-effectiveness of linagliptin for a lifetime outcome was favourable in Japan. However, the results must be interpreted cautiously because of the noninferiority trial data source, which might cause ICER variations for each parameter. Electronic Supplementary Material The online version of this article (10.1007/s13300-020-00852-8) contains supplementary material, which is available to authorized users.
- Published
- 2020
14. Systematic Literature Review of DPP-4 Inhibitors in Patients with Type 2 Diabetes Mellitus and Renal Impairment.
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Thomas, Merlin, Paldánius, Päivi, Ayyagari, Rajeev, Ong, Siew, and Groop, Per-Henrik
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PEOPLE with diabetes , *CD26 antigen , *KIDNEY diseases , *GLYCOSYLATED hemoglobin , *PLACEBOS - Abstract
Introduction: Dipeptidyl peptidase-4 (DPP-4) inhibitors are widely used in the management of patients with type 2 diabetes mellitus (T2DM) and renal impairment (RI). A systematic literature review was performed to compare the efficacy and safety of DPP-4 inhibitors in patients with T2DM and RI. Methods: We searched EMBASE, MEDLINE, and the Cochrane Central Register of Controlled Trials (cut-off, June 2015) to identify ≥12-week, randomized, placebo-controlled trials on DPP-4 inhibitors in ≥50 patients with T2DM and RI. Outcomes of interest included change in glycated hemoglobin (HbA1c), overall safety, and incidence of hypoglycemic events (HEs). Results: Seven trials of ≤52-54 weeks duration were retrieved, which included one study each on vildagliptin, saxagliptin, and sitagliptin, two on linagliptin, and the remaining two were extension studies of vildagliptin and saxagliptin. Majority of patients were on insulin at baseline (53-86%), except in the sitagliptin study, where approximately 11% received insulin during the placebo-controlled phase. After 52 weeks, vildagliptin and saxagliptin reduced HbA1c levels by 0.6-0.7% (baseline 7.8-8.4%) versus placebo in the overall population. HbA1c reductions were similar at weeks 12 and 52. In the 12-week, placebo-controlled phase, sitagliptin and linagliptin reduced mean HbA1c by approximately 0.4% (baseline 7.7-8.1%) versus placebo. Rates of HEs with DPP-4 inhibitors were not significantly different versus placebo in any study. Rates of adverse events (AEs) and changes involving renal function were similar in the active- and placebo-treated groups. Conclusion: These results suggest that DPP-4 inhibitors have the potential to improve glycemic control in patients with RI without increasing the risk of HEs or overall AEs. Funding: Novartis Pharma AG. [ABSTRACT FROM AUTHOR]
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- 2016
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15. The Effect of Linagliptin versus Metformin Treatment-Related Quality of Life in Patients with Type 2 Diabetes Mellitus
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Junko Sato, Miho Shimizu, Hirotaka Watada, Daijiro Yasuda, Toru Hiyoshi, Hiroko Chimori, Kazuo Ikeda, Hareaki Yamamto, Hidenori Yoshii, Tomoya Mita, and Yuichi Kojima
- Subjects
medicine.medical_specialty ,Randomization ,endocrine system diseases ,Endocrinology, Diabetes and Metabolism ,Treatment-related quality of life ,030209 endocrinology & metabolism ,Linagliptin ,030204 cardiovascular system & hematology ,03 medical and health sciences ,0302 clinical medicine ,Quality of life ,Diabetes mellitus ,Internal medicine ,Type 2 diabetes mellitus ,Internal Medicine ,medicine ,Adverse effect ,Glycemic ,Original Research ,business.industry ,Questionnaire ,Type 2 Diabetes Mellitus ,medicine.disease ,Metformin ,business ,medicine.drug - Abstract
Introduction There have been no studies directly comparing the effect of dipeptidyl peptidase-4 inhibitors with that of metformin on treatment-related quality of life (QOL) when used as first-line therapy in patients with type 2 diabetes mellitus (T2DM). Methods This study is a prospective, randomized, open-label, multicenter, parallel-group, comparative study. Forty-four participants who failed to achieve target glycemic control with diet and exercise therapy were randomly allocated to receive linagliptin or metformin therapy. We compared treatment-related QOL among the two groups using the Oral Hypoglycemic Agent Questionnaire, version 2 (OHA-Q version 2) and the self-administered Diabetes Therapy-Related QOL (DTR-QOL) questionnaire. Results After randomization, 21 patients in the linagliptin group and 22 patients in the metformin treatment group were included in the full analysis set. Biochemical parameters, incidence of adverse effects, and rate of adherence to medication were comparable between the two groups. Over the 24-week treatment period, no significant differences in overall OHA-Q scores between the groups were observed, although the subscale 1 (treatment convenience) score was significantly higher in the linagliptin group than in the metformin group. The overall DTR-QOL score did not differ between the two groups; however, the DTR-QOL scores significantly improved after 24 weeks of linagliptin treatment, but not after metformin treatment. Conclusion We did not find significantly better treatment-related QOL with linagliptin among Japanese patients with T2DM. In terms of treatment convenience, our data showed that linagliptin was superior to metformin. Funding This study was financially supported by Nippon Boehringer Ingelheim Co., Ltd. and Eli Lilly and Company. The journal’s article processing fees were covered by a research fund from Juntendo University. Clinical Trial Registration UMIN000022953. Electronic Supplementary Material The online version of this article (10.1007/s13300-018-0539-5) contains supplementary material, which is available to authorized users.
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- 2018
16. Study Protocol for the Initial Choice of DPP-4 Inhibitor in Japanese Patients with Type 2 diabetes Mellitus: Effect of Linagliptin on QOL (INTEL-QOL) Trial
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Junko Sato, Hidenori Yoshii, Tomoya Mita, Hirotaka Watada, Kazuo Ikeda, Toru Hiyoshi, and Hiroko Chimori
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medicine.medical_specialty ,Treatment-related quality of life ,Endocrinology, Diabetes and Metabolism ,Linagliptin ,030209 endocrinology & metabolism ,Study Protocol ,03 medical and health sciences ,0302 clinical medicine ,Quality of life ,Diabetes management ,Diabetes mellitus ,Internal medicine ,Type 2 diabetes mellitus ,Internal Medicine ,medicine ,030212 general & internal medicine ,Adverse effect ,Glycemic ,Questionnaire ,business.industry ,Type 2 Diabetes Mellitus ,medicine.disease ,Metformin ,business ,medicine.drug - Abstract
Introduction Consideration of treatment-related quality of life (QOL) is important in diabetes management. However, no studies have compared the influence of dipeptidyl peptidase-4 inhibitors versus metformin on treatment-related QOL when used as first-line therapy in patients with type 2 diabetes mellitus. Methods This study is a prospective, randomized, open-label, multicenter, parallel-group, comparative study. Between June 2016 and December 2017, 44 participants who failed to achieve glycemic control despite diet and exercise therapy were recruited at 14 clinics and randomly allocated to linagliptin or metformin therapy. Treatment-related QOL was assessed with the Oral Hypoglycemic Agent Questionnaire, version 2 (OHA-Q ver. 2) and the self-administered Diabetes Therapy-Related QOL (DTR-QOL) questionnaire. The primary study outcome is the difference in total OHA-Q ver. 2 score between the two treatment groups at the end of the study. The secondary outcomes include differences in the scores for each OHA-Q ver. 2 subscale between the two treatment groups at the end of the study, change in total DTR-QOL score and for each domain from baseline to the end of treatment, changes in glycemic control, and adverse events. Planned outcome The present study is designed to assess the effects of linagliptin on the treatment-related QOL. Results will be available in the near future. Study findings are expected to provide useful information on how to maintain or improve QOL in patients with type 2 diabetes mellitus treated with insulin. Funding Nippon Boehringer Ingelheim Co., Ltd. and Eli Lilly and Company. Clinical trial registration UMIN000022953.
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- 2018
17. Systematic Literature Review of DPP-4 Inhibitors in Patients with Type 2 Diabetes Mellitus and Renal Impairment
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S.H. Ong, Päivi M. Paldánius, Rajeev Ayyagari, Merlin C. Thomas, Per-Henrik Groop, Clinicum, Per Henrik Groop / Principal Investigator, and Department of Medicine
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CHRONIC KIDNEY-DISEASE ,medicine.medical_specialty ,animal structures ,endocrine system diseases ,LONG-TERM ,Endocrinology, Diabetes and Metabolism ,BLOOD-PRESSURE ,Linagliptin ,030209 endocrinology & metabolism ,SEVERE HYPOGLYCEMIA ,Review ,Saxagliptin ,Pharmacology ,DOUBLE-BLIND ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,QUALITY-OF-LIFE ,GLYCEMIC CONTROL ,DPP-4 inhibitors ,Diabetes mellitus ,Internal medicine ,Type 2 diabetes mellitus ,Internal Medicine ,Sitagliptin ,Medicine ,Vildagliptin ,030212 general & internal medicine ,business.industry ,nutritional and metabolic diseases ,Type 2 Diabetes Mellitus ,EFFICACY ,medicine.disease ,3. Good health ,Blood pressure ,Systematic review ,chemistry ,SAFETY ,3121 General medicine, internal medicine and other clinical medicine ,business ,medicine.drug - Abstract
Introduction Dipeptidyl peptidase-4 (DPP-4) inhibitors are widely used in the management of patients with type 2 diabetes mellitus (T2DM) and renal impairment (RI). A systematic literature review was performed to compare the efficacy and safety of DPP-4 inhibitors in patients with T2DM and RI. Methods We searched EMBASE, MEDLINE, and the Cochrane Central Register of Controlled Trials (cut-off, June 2015) to identify ≥12-week, randomized, placebo-controlled trials on DPP-4 inhibitors in ≥50 patients with T2DM and RI. Outcomes of interest included change in glycated hemoglobin (HbA1c), overall safety, and incidence of hypoglycemic events (HEs). Results Seven trials of ≤52–54 weeks duration were retrieved, which included one study each on vildagliptin, saxagliptin, and sitagliptin, two on linagliptin, and the remaining two were extension studies of vildagliptin and saxagliptin. Majority of patients were on insulin at baseline (53–86%), except in the sitagliptin study, where approximately 11% received insulin during the placebo-controlled phase. After 52 weeks, vildagliptin and saxagliptin reduced HbA1c levels by 0.6–0.7% (baseline 7.8–8.4%) versus placebo in the overall population. HbA1c reductions were similar at weeks 12 and 52. In the 12-week, placebo-controlled phase, sitagliptin and linagliptin reduced mean HbA1c by approximately 0.4% (baseline 7.7–8.1%) versus placebo. Rates of HEs with DPP-4 inhibitors were not significantly different versus placebo in any study. Rates of adverse events (AEs) and changes involving renal function were similar in the active- and placebo-treated groups. Conclusion These results suggest that DPP-4 inhibitors have the potential to improve glycemic control in patients with RI without increasing the risk of HEs or overall AEs. Funding Novartis Pharma AG. Electronic supplementary material The online version of this article (doi:10.1007/s13300-016-0189-4) contains supplementary material, which is available to authorized users.
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- 2016
18. Comparative Effectiveness of Dipeptidylpeptidase-4 Inhibitors in Type 2 Diabetes: A Systematic Review and Mixed Treatment Comparison
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Paul Craddy, H.J. Palin, and K. Ian Johnson
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medicine.medical_specialty ,Endocrinology, Diabetes and Metabolism ,Linagliptin ,Review ,Type 2 diabetes ,Saxagliptin ,chemistry.chemical_compound ,Mixed treatment comparison ,Internal medicine ,Diabetes mellitus ,Type 2 diabetes mellitus ,Internal Medicine ,medicine ,DPP-4 inhibitor ,Sitagliptin ,Alogliptin ,Glycemic ,Vildagliptin ,business.industry ,Type 2 Diabetes Mellitus ,Glycosylated hemoglobin ,medicine.disease ,chemistry ,business ,medicine.drug - Abstract
Objective To compare the safety and efficacy of the dipeptidylpeptidase-4 (DPP-4) inhibitors in patients with type 2 diabetes and inadequate glycemic control. Design Systematic review of randomized controlled trials (RCTs), health economic evaluation studies, systematic reviews, and meta-analyses, followed by primary Bayesian mixed treatment comparison meta-analyses (MTCs), and secondary frequentist direct-comparison meta-analyses using a random-effects model. Outcomes were reported as weighted mean change from baseline, or odds ratio (OR) with 95% credible interval. Data sources MEDLINE, MEDLINE In-Process, EMBASE, and BIOSIS via Dialog ProQuest; Cochrane Central Register of Controlled Trials and Cochrane Database of Systematic Reviews via EBSCO; four diabetes and two technical congress abstracts; and health technology assessment organization websites. Eligibility criteria Patients with type 2 diabetes and inadequate glycemic control receiving any pharmacological anti-diabetic treatment. Data extraction and analysis Title/abstracts were reviewed for eligibility, followed by full-text review of publications remaining after first pass. A three-person team filtered articles and an independent reviewer checked a random selection (10%) of filtered articles. Data extraction and quality assessment of studies were also independently reviewed. Five DPP-4 inhibitors (alogliptin, linagliptin, saxagliptin, sitagliptin, and vildagliptin) were compared via meta-analysis (where data were available) as monotherapy, dual therapy (plus metformin, sulfonylurea, pioglitazone, or insulin), and triple therapy (plus metformin/sulfonylurea). Results The review identified 6,601 articles; 163 met inclusion criteria and 85 publications from 83 RCTs contained sufficient or appropriate data for analysis. MTCs demonstrated no differences between DPP-4 inhibitors in mean change from baseline in glycosylated hemoglobin (HbA1c) or body weight, or the proportions of patients achieving HbA1c
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- 2014
19. Comparative Effectiveness of Adding Alogliptin to Metformin Plus Sulfonylurea with Other DPP-4 Inhibitors in Type 2 Diabetes: A Systematic Review and Network Meta-Analysis
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Jorge Puelles, Amanda J. Strickson, Stephen Kay, Ross Selby, Keith Tolley, and Eugene Benson
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Oncology ,medicine.medical_specialty ,endocrine system diseases ,Endocrinology, Diabetes and Metabolism ,Population ,030209 endocrinology & metabolism ,Review ,Saxagliptin ,Pharmacology ,Linagliptin ,law.invention ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Randomized controlled trial ,law ,Internal medicine ,Type 2 diabetes mellitus ,Internal Medicine ,medicine ,DPP-4 inhibitor ,Vildagliptin ,030212 general & internal medicine ,Network meta-analysis ,Triple therapy ,education ,education.field_of_study ,Alogliptin once daily ,business.industry ,nutritional and metabolic diseases ,Metformin ,chemistry ,Sitagliptin ,Systematic review ,business ,Alogliptin ,medicine.drug - Abstract
Introduction Alogliptin is an oral antihyperglycemic agent that is a selective inhibitor of the enzyme dipeptidyl peptidase-4 (DPP-4), approved for the treatment of type 2 diabetes mellitus (T2DM). There currently exists no comparative data to support the use of alogliptin in combination with metformin (met) and sulfonylurea (SU). A decision-focused network meta-analysis (NMA) was performed to compare the relative efficacy and safety of alogliptin 25 mg once daily to other DPP-4 inhibitors as part of a triple therapy regimen for patients inadequately controlled on metformin and SU dual therapy. Methods A systematic literature review was conducted to identify published papers of randomized controlled trials (RCTs) that compared alogliptin with other DPP-4 inhibitors (linagliptin, saxagliptin, sitagliptin, and vildagliptin) at their Summary of Product Characteristics (SmPC) recommended daily doses, added on to metformin and SU. Comprehensive comparative analysis involving frequentist meta-analysis and Bayesian NMA compared alogliptin to each DPP-4 inhibitor separately and collectively as a group. Quasi-random effect models were introduced when random effect models could not be estimated. Results The review identified 2186 articles, and 94 full-text articles were assessed for eligibility. Eight RCTs contained appropriate data for inclusion in the NMA. All analyses over all trial population sets produced very similar results, and show that alogliptin 25 mg is as least as effective (as measured by change in HbA1c from baseline, but supported by other outcome measures: change in body weight and FPG from baseline) and safe (as measured by incidence of hypoglycemia and adverse events leading to study discontinuation) as all the other DPP-4 inhibitors in triple therapy. Conclusion This decision-focused systematic review and NMA demonstrated alogliptin 25 mg daily to have similar efficacy and safety compared to other DPP-4 inhibitors, for the treatment of T2DM in adults inadequately controlled on metformin and SU. (Funded by Takeda Development Centre Americas; EXAMINE ClinicalTrials.gov number, NCT00968708). Electronic supplementary material The online version of this article (doi:10.1007/s13300-017-0245-8) contains supplementary material, which is available to authorized users.
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