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Abstract Background Due to the progressive decline in β-cell function, it is often necessary to utilize multiple agents with complementary mechanisms of action to address various facets and achieve glycemic control. Thus, this study aimed to evaluate the efficacy and safety of a fixed-dose combination (FDC) of metformin/sitagliptin/pioglitazone (MSP) therapy vs. metformin/sitagliptin (MS) in type 2 diabetes mellitus (T2DM). Methods In this phase 3, multicenter, double-blind study, patients with T2DM who exhibited inadequate glycemic control with HbA1c of 8.0–11.0% while taking ≥1500 mg/day metformin for at least 6 weeks were randomized to receive either FDC of MSP (1000/100/15 mg) or MS (1000/100 mg) per day for 24 weeks. The primary outcome measure was the change in HbA1c, and secondary outcomes included changes in fasting plasma glucose (FPG), postprandial plasma glucose (PPG), and body weight from baseline to 24 weeks along with safety and tolerability. Results Among the 236 patients randomized, 207 (87.71%) successfully completed the study. All baseline characteristics were comparable between the FDC of MSP and MS groups. There was a subsequent significant reduction of HbA1c in FDC of MSP (− 1.64) vs. MS (− 1.32); between groups was [− 0.32% (95% CI, − 0.59, − 0.05)], P = 0.0208. Similar reductions were found in FPG [− 13.2 mg/dL (95% CI, − 22.86, − 3.71)], P = 0.0068, and PPG [− 20.83 mg/dL (95% CI, − 34.11, − 7.55)], P = 0.0023. There were no significant changes in body weight. A total of 27 adverse effects (AEs) and one severe AE were reported, none of which were related to the study drug. Conclusion The FDC of MSP demonstrated significant efficacy in managing glycemic indices and could serve as a valuable tool for physicians in the management of Indian patients with T2DM. Trial registration Clinical Trials Registry of India, CTRI/2021/10/037461.

Objectives: Somatrogon is a long-acting recombinant human growth hormone used to treat patients with paediatric growth hormone deficiency (pGHD). This global phase 3 study compared the efficacy and safety of once-weekly somatrogon with once-daily somatropin in children with GHD., Methods: Prepubertal patients were randomized 1:1 to once-weekly somatrogon (0.66 mg/kg/week) or once-daily somatropin (0.24 mg/kg/week) for 12 months. The primary endpoint was height velocity (HV) at month 12; secondary endpoints included HV at month 6 and change in height standard deviation score (SDS) at months 6 and 12 and insulin-like growth factor 1 (IGF-1) SDS., Results: This post hoc subgroup analysis focused specifically on Asian children (somatrogon: n=24 and mean age=7.76 years; somatropin: n=21 and mean age=8.10 years) across eight countries. Mean HV at month 12 was 10.95 cm/year (somatrogon) and 9.58 cm/year (somatropin); the treatment difference of 1.38 cm/year favoured somatrogon. The lower bound of the two-sided 95 % CI of the treatment difference (somatrogon-somatropin) was -0.20, similar to the overall study population (-0.24). Compared with the somatropin group, the somatrogon group had numerically higher HV at month 6 (8.31 vs. 11.23 cm/year); a similar trend was observed for height SDS and IGF-1 SDS at months 6 and 12. Safety and tolerability were similar between treatment groups; adverse events occurred in 83 % of somatrogon-treated children and 76 % of somatropin-treated children., Conclusions: This subgroup analysis demonstrated that somatrogon efficacy and safety in Asian children were consistent with the overall study population, where once-weekly somatrogon was non-inferior to once-daily somatropin. Clinicaltrials.gov: NCT02968004., (© 2024 the author(s), published by De Gruyter, Berlin/Boston.)

Competing Interests: Competing interests: None declared.

Objective: This study was done to analyse the demographic profile and presentation of diabetes in Central India., Design: Data was collected for this cross-sectional study from an electronic diabetes registry from 2014 to 2019. Demographic details, patient history and presence or absence of co-morbid conditions, duration of diabetes, age of onset of diabetes, drug history, personal history, presence of micro and/or macrovascular complications and investigations done were obtained., Statistical Analysis: The association between each factor and the outcome was studied in terms of prevalence ratio (PR) using the R-3.0.0 programming (R Foundation for Statistical Computing, Vienna, Austria) language. Statistical significance was evaluated at a 5% level., Results: Among 12,434 patients, 54.95% were below 50 years and 45.05% were above 50 years. 50.21% were females and 49.79% were males. The mean age was 47.49 ± 14.78 years and the mean body mass index (BMI) was 26.85 ± 5.19 kg/m 2 with 62.29% of obese patients (>25 kg/m 2 ). The mean overall duration of diabetes was 7.64 ± 7.63 years. Mean Glycosylated Haemoglobin (HbA1c) in patients <=50 years was 8.60 ± 2.63 and 8.90 ± 1.91 for over 50. 65.59% had uncontrolled blood sugars. 25.19% of patients had hypertension and 18.1% had dyslipidaemia. Coronary artery disease (CAD), nephropathy, neuropathy and retinopathy were observed in 21.49%, 9.60%, 33.65% and 14.65%, respectively. The adjusted PR of cardiovascular disease (CVD) was 5.374 times higher for patients over 50 ( P < 0.0001); 3.775 times higher for males ( P < 0.0001), 1.64 times higher for patients with BMI >25 kg/m 2 ( P < 0.0001) and 3.643 times higher in hypertensive cases ( P < 0.0001). Similar associations were observed with nephropathy, neuropathy and retinopathy., Conclusion: From a large population study on diabetes, it was found a majority of the type 2 diabetes mellitus (T2DM) cases (65%) are sub-optimally controlled with HbA1c levels. Also, microvascular complications were related to the sub-optimal glycaemic control, but not the macro-vascular complications., Competing Interests: There are no conflicts of interest., (Copyright: © 2022 Indian Journal of Endocrinology and Metabolism.)

Background: Metformin is the first-line treatment for type 2 diabetes mellitus (T2DM), but many patients either cannot tolerate it or cannot achieve glycemic control with metformin alone, so treatment with other glucose-lowering agents in combination with metformin is frequently required. Remogliflozin etabonate, a novel agent, is an orally bioavailable prodrug of remogliflozin, which is a potent and selective sodium-glucose co-transporter-2 inhibitor., Objective: Our objective was to evaluate the efficacy and safety of remogliflozin etabonate compared with dapagliflozin in subjects with T2DM in whom a stable dose of metformin as monotherapy was providing inadequate glycemic control., Methods: A 24-week randomized, double-blind, double-dummy, active-controlled, three-arm, parallel-group, multicenter, phase III study was conducted in India. Patients aged ≥ 18 and ≤ 65 years diagnosed with T2DM, receiving metformin ≥ 1500 mg/day, and with glycated hemoglobin (HbA1c) levels ≥ 7 to ≤ 10% at screening were randomized into three groups. Every patient received metformin ≥ 1500 mg and either remogliflozin etabonate 100 mg twice daily (BID) (group 1, n = 225) or remogliflozin etabonate 250 mg BID (group 2, n = 241) or dapagliflozin 10 mg once daily (QD) in the morning and placebo QD in the evening (group 3, n = 146). The patients were followed-up at weeks 1 and 4 and at 4-week intervals thereafter until week 24. The endpoints included mean change in HbA1c (primary endpoint, noninferiority margin = 0.35), fasting plasma glucose (FPG), postprandial plasma glucose (PPG), bodyweight, blood pressure, and fasting lipids. Treatment-emergent adverse events (TEAEs), safety laboratory values, electrocardiogram, and vital signs were evaluated., Results: Of 612 randomized patients, 167 (group 1), 175 (group 2), and 103 (group 3) patients with comparable baseline characteristics completed the study. Mean change ± standard error (SE) in HbA1c from baseline to week 24 was - 0.72 ± 0.09, - 0.77 ± 0.09, and - 0.58 ± 0.12% in groups 1, 2, and 3, respectively. The difference in mean HbA1c of group 1 versus group 3 (- 0.14%, 90% confidence interval [CI] - 0.38 to 0.10) and group 2 versus group 3 (- 0.19%; 90% CI - 0.42 to 0.05) was noninferior to that in group 3 (p < 0.001). No significant difference was found between group 1 or group 2 and group 3 in change in FPG, PPG, and bodyweight. The overall incidence of TEAEs was comparable across study groups (group 1 = 32.6%, group 2 = 34.4%, group 3 = 29.5%), including adverse events (AEs) of special interest (hypoglycemic events, urinary tract infection, genital fungal infection). Most TEAEs were mild to moderate in intensity, and no severe AEs were reported., Conclusion: This study demonstrated the noninferiority of remogliflozin etabonate 100 and 250 mg compared with dapagliflozin, from the first analysis of an initial 612 patients. Remogliflozin etabonate therefore may be considered an effective and well-tolerated alternative treatment option for glycemic control in T2DM., Trial Registration: CTRI/2017/07/009121.

Aim: This study aimed to assess efficacy and safety of evogliptin versus sitagliptin, when added to background metformin therapy in Indian patients with uncontrolled type 2 diabetes., Method: Overall, 184 patients with uncontrolled type 2 diabetes (7% ≤ HbA 1c  < 10%) receiving ≥8 weeks of stable metformin monotherapy (≥1 g/day), were randomized to receive add-on treatment (evogliptin 5 mg or sitagliptin 100 mg) for 24 weeks. Primary endpoint was change in HbA 1c from baseline to 12 weeks (non-inferiority margin: <0.35)., Results: Mean reductions in HbA1c at 12 weeks in evogliptin- and sitagliptin-treated patients were -0.37 (1.06) and -0.32 (1.14), respectively. The adjusted mean difference between treatment groups was -0.022 (95% CI: -0.374, 0.330; P = 0.901), that demonstrated non-inferiority. Reductions in FPG and PPG were similar between evogliptin and sitagliptin at 12 and 24 weeks. Changes in body weight were comparable between the treatment groups. Patients achieving target HbA 1c  < 7.0% (evogliptin, 26.7% vs. sitagliptin, 20%) was almost equal in both groups. Treatment-emergent adverse events occured in 52 patients (evogliptin, 25% and sitagliptin, 31.5%) and were generally mild., Conclusions: Evogliptin was non-inferior to sitagliptin in HbA 1c reduction. It effectively improved glycemic control and was well tolerated in type 2 diabetes patients inadequately controlled by metformin alone., (Copyright © 2019 Elsevier B.V. All rights reserved.)