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Sodium glucose cotransporter inhibitor (SGLTi) drugs have been widely used in clinical practice. In addition to their benefits in hyperglycemia, heart failure (HF), and kidney disease, their effects on obesity, metabolic dysfunction-associated steatotic liver disease (MASLD, formerly named nonalcoholic fatty liver disease [NAFLD]), polycystic ovarian syndrome (PCOS), abnormal lipid metabolism, hyperuricemia, obstructive sleep apnea syndrome (OSAS), anemia, and syndrome of inappropriate antidiuresis (SIAD, formerly named syndrome of inappropriate antidiuretic hormone [SIADH]) have been explored. In this review, we searched the data of clinical randomized controlled trials (RCTs) and meta-analyses of SGLTis in patients with diabetes from the PubMed library between January 1, 2020, and February 1, 2024. According to our review, certain SGLTis exhibit relatively superior clinical safety and effectiveness for treating the abovementioned diseases. Proper utilization of SGLTis in these patients can provide additional medication options for patients with different disease scenarios. However, studies of SGLTis in these diseases are relatively rare, with shortcomings such as small sample sizes and short intervention periods. Therefore, further large-scale, long-term, well-designed studies are needed to clarify the findings., (© 2024 Pharmacotherapy Publications, Inc.)

Intensive glucose therapy can protect the retina of individuals with diabetes, but it is unknown if it provides the same protection to patients with different severity of diabetic retinopathy (DR). We finally included DR-related studies involving intensive glucose control with large sample size and long follow-up time, including five large and high-quality randomized clinical trials (RCTs): DCCT, UKPDS, ACCORD, AdRem, and VADT. With DCCT as a reference, we supposed a DR severity threshold that is verified by other RCTs then. We found that individuals who have DR lesions that are equivalent to or less severe than moderate NPDR achieve benefits for the retina by intensive glycemic control. However, these are realized only if the HbA1c in type 1 or type 2 diabetic patients is reduced at least by 0.8% versus the control group or it is reduced to <7% and >3 years of intensive glucose control is required. If the severity of DR lesions is worse than moderate NPDR, intensive glycemic control may not bring benefits., Competing Interests: The authors declare that they have no conflict of interest., (Copyright © 2020 Yuqi Liu et al.)

Objective: This study aimed to investigate the changes in inflammatory biomarkers between newly diagnosed type 2 diabetes (T2DM) patients under one-year acarbose treatments and those under metformin managements., Methods: Seventy patients with newly diagnosed T2DM and 32 volunteers with normal glucose tolerance (normal controls, NCs) were enrolled. Seventy patients with T2DM were randomly assigned to two subgroups and treated with acarbose (n=34) or metformin (n=36) for 1 year. Blood glucose, insulin, glycosylated hemoglobin (A1C), triglyceride (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and inflammatory biomarker levels (interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-2 (IL-2), and ferritin) were detected at 0, 6 and 12 months., Results: After adjusting for sex, the waist-to-hip ratio (WHR) and body mass index (BMI), higher fasting plasma glucose (FPG), standard meal test 1/2 hr and 2 hr glucose, TG, TC, LDL-C, IL-6, TNF-α, IL-2 and ferritin levels were observed in T2DM group than in NCs ( P <0.05). After 6 months of treatment, TNF-α levels were significantly decreased in both subgroups, and IL-6 and ferritin levels were significantly decreased after 12 months ( P <0.05). However, no significant differences in the IL-6, TNF-α and ferritin levels were observed between the two subgroups. Moreover, significantly higher IL-6 and TNF-α levels were detected in the T2DM group than in NCs after 12 months of treatment ( P <0.05)., Conclusion: Patients with newly diagnosed T2DM exhibited a marked chronic inflammatory state characterized by increased IL-6, TNF-α, IL-1β, IL-2 and ferritin levels. After 1 year of treatment with acarbose or metformin, IL-6, TNF-α, IL-1β and ferritin levels were significantly decreased compared with the baseline. The anti-inflammatory effects of acarbose and metformin were comparable and required a long-term treatment (1 year), but the characteristics were different. Further investigations are needed to determine whether this effect was independent of the hypoglycemic effects., Competing Interests: The authors report no conflicts of interest in this work.

Diabetics have higher morbidity and mortality in cardiovascular disease (CVD). A variety of antidiabetic agents are available for clinical choice. Cardiovascular (CV) safety assessment of these agents is crucial in addition to hypoglycemic effect before clinical prescription. Adenosine 5'-monophosphate-activated protein kinase (AMPK) is an important cell energy sensor, which plays an important role in regulating myocardial energy metabolism, reducing ischemia and ischemia/reperfusion (I/R) injury, improving heart failure (HF) and ventricular remodeling, ameliorating vascular endothelial dysfunction, antichronic inflammation, anti-apoptosis, and regulating autophagy. In this review, we summarized the effects of antidiabetic agents to CVD according to basic and clinical research evidence and put emphasis on whether these agents can play roles in CV system through AMPK-dependent signaling pathways. Metformin has displayed definite CV benefits related to AMPK. Sodium-glucose cotransporter 2 inhibitors also demonstrate sufficient clinical evidence for CV protection, but the mechanisms need further exploration. Glucagon-likepeptide1 analogs, dipeptidyl peptidase-4 inhibitors, α-glucosidase inhibitors and thiazolidinediones also show some AMPK-dependent CV benefits. Sulfonylureas and meglitinides may be unfavorable to CV system. AMPK is becoming a promising target for the treatment of diabetes, metabolic syndrome and CVD. But there are still some questions to be answered., (© 2019 The Author(s).)

Aims: A systematic review and meta-analysis was conducted to evaluate the clinical efficacy and safety of sodium-glucose cotransporter 2 (SGLT2) inhibitors in patients with type 2 diabetes (T2D) and moderate renal function impairment., Methods: Embase, Medline, and Cochrane Central were searched, and randomized controlled trials comparing SGLT2 inhibitors to placebos and other drugs for T2D were collected., Results: Seven RCTs with a total of 3307 participants were included, and the overall bias was low. In the patients with T2D and moderate renal function impairment (30 ml/min/1.73 m 2 ≤ estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m 2 ) compared with the placebo, SGLT2 inhibitors improved HbA1c significantly (WMD, -0.23%; 95% CI: -0.38 to -0.08), presented a lower incidence of hypoglycemia (30.1% vs. 34.6%; RR, 0.85; 95% CI: 0.76 to 0.96), led to the reduction of eGFR (WMD, -1.74 ml/min/1.73 m 2 ; 95% CI: -3.45 to -0.03), resulted in an obvious reduction in body weight (WMD, -1.45 kg; 95% CI: -2.01 to -0.89), and presented a similar risk of urinary tract infection and genital infection., Conclusions: SGLT2 inhibitors are safe, but mildly reduce the HbA1c level. The clinical significance of SGLT2 inhibitors in the target population was limited., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are desirable for diabetes, especially in patients with overweight/obesity. We aimed to determine whether GLP-1RAs exhibit different glucose-lowering efficacies between Asian type 2 diabetes (T2D) patients with and without overweight/obesity. Randomized controlled trials were searched in EMBASE, MEDLINE, CENTRAL, and ClinicalTrials.gov. Studies published in English with treatment duration ≥12 weeks and information on HbA1c changes were included. The studies were divided into normal body mass index (BMI) and overweight/obese groups according to baseline BMI. Among 3190 searched studies, 20 trials were included in the meta-analysis. The standardized mean differences in HbA1c change, fasting glucose change, and postprandial glucose change were equivalent between normal BMI and overweight/obese studies (p > 0.05). The relative risk of HbA1c < 6.5% target achievement in normal BMI trials (7.93; 95% confidence interval: 3.27, 19.20) was superior to that in overweight/obesity trials (2.23; 1.67, 2.97), with a significant difference (p = 0.020). Body weight loss (p = 0.572) and hypoglycemic risk(p = 0.920) were similar in the two groups. The glucose-lowering effects of GLP-1RAs were equivalent among Asian T2D patients. With their advantages for weight-loss or weight-maintenance, GLP-1RAs are optimal medicines for Asian T2D patients with and without overweight/obesity.

Objectives: We aim to conduct a meta-analysis, by stratifying diabetic patients with or without clinical cardiovascular diseases (CVD), to explore whether there are different cardiovascular effects of dipeptidyl peptidase-4 inhibitors (DPP-4is) on these two different classes of diabetic patients., Methods: We searchedMedline,Embase, theCochrane Libraryand ClinicalTrials.gov for relevant randomized controlled trials (RCTs). The included trials are divided into CVD (+) trials (subjects with established CVD), and CVD (-) trials (subjects with no CVD). We use all-cause mortality and cardiovascular outcomes as primary endpoints., Results: (1) Three CVD (+) trials were included and 36,895 subjects were enrolled with a mean follow-up duration of 127.1 weeks. The pooled results showed that DPP-4is treatment, compared with the placebo, did not significantly affect all-cause mortality (RR, 1.03; 95% CI, 0.95 to 1.11), cardiovascular death (1.01, 0.91 to 1.12), myocardial infarction (0.98, 0.88 to 1.08) or stroke (1.02, 0.88 to 1.18) in diabetic patients with coexisting CVD history; however, it significantly increased the risk of heart failure (1.14, 1.01 to 1.27) in this population. 2) Thirty-five CVD (-) trials were included, and 29,600 patients were enrolled with a mean follow-up duration of 77.8 weeks. The analysis comparing DPP-4is with the placebo control showed that DPP-4is treatment did not significantly affect the risk of all-cause mortality or cardiovascular outcomes in diabetic patients free of CVD history. However, when compared with the active control, the pooling data showed that DPP-4is had a significant reduction on the risk of stroke (0.58, 0.34 to 0.99) but did not significantly affect the risk of all-cause mortality and other cardiovascular outcomes., Conclusion: DPP-4is may have no cardiovascular protective effects in diabetic patients with coexisting CVD, while there is a lack of definitive evidence supporting the cardiovascular benefits of DPP-4is treatment among diabetic patients free of CVD history.

Purpose: Retrospective, case-control studies and prospective randomized controlled trials (RCTs) on insulin treatment for diabetic patients yielded contradictory mortality and cardiovascular outcomes. We aimed to evaluate the effects of insulin versus oral hypoglycemic agents (OHAs) on all-cause mortality and cardiovascular outcomes in patients with type 2 diabetes (T2D)., Methods: We searched Medline, Embase, Cochrane Central Register of Controlled Trials, Chinese Biological Medicine Database, China National Knowledge Infrastructure, Chinese Technical Periodicals, and Wanfang Data, up to July 10, 2015, for RCTs on insulin and OHAs that assessed all-cause mortality and/or cardiovascular death as primary end points. We derived pooled risk ratios (RRs) as summary statistics., Results: Three trials were included in which 7649 patients received insulin and 8322 received OHAs, with mean (SD) diabetes duration of 5.0 (6.2) and 4.4 (5.9) years, respectively. Insulin did not differ from OHAs in all-cause mortality (RR = 1.00; 95% CI, 0.93-1.07), cardiovascular death (RR = 1.00; 95% CI, 0.91-1.09), myocardial infarction (RR = 1.04; 95% CI, 0.93-1.16), angina (RR = 0.97; 95% CI, 0.88-1.06), sudden death (RR = 1.02; 95% CI, 0.66-1.56), or stroke (RR = 1.01; 95% CI, 0.88-1.15). Insulin reduced the risk of heart failure compared with OHAs (RR = 0.87; 95% CI, 0.75-0.99). In the subgroup of secondary prevention of cardiovascular diseases (CVDs) or very high risk of CVDs, insulin did not differ from OHAs in all-cause mortality (RR = 0.99; 95% CI, 0.92-1.07), cardiovascular death (RR = 0.99; 95% CI, 0.90-1.09), myocardial infarction (RR = 1.01; 95% CI, 0.88-1.15), heart failure (RR = 0.69; 95% CI, 0.34-1.40), or stroke (RR = 1.05; 95% CI, 0.90-1.21)., Implications: Insulin did not provide a clear benefit over OHAs in all-cause mortality or cardiovascular outcomes in the patients with T2D. Insulin therapy has many shortcomings, including inconvenience (injection, strict blood glucose monitoring), hypoglycemia, and obvious weight gain. Thus, we conclude that no robust evidence supports the active use of insulin for this population at present., (Copyright © 2016 Elsevier HS Journals, Inc. All rights reserved.)

A meta-analysis was conducted to assess the clinical efficacy and safety of dulaglutide in patients with type 2 diabetes mellitus (T2DM). Medline, Embase, Cochrane Library and www. clinicaltrials. gov (up to February 15(th), 2015) were searched. Randomized controlled trials comparing dulaglutide to other drugs for T2DM were collected. Twelve RCTs were included, and the overall bias was low. As the monotherapy, compared with control (placebo, metformin and liraglutide), dulaglutide resulted in a significant reduction in HbA1c (WMD, -0.68%; 95% CI, -0.95 to -0.40), FPG (WMD, -0.90 mmol/L; 95% CI, -1.28 to -0.52), a similar risk of hypoglycemia (7.8% vs. 10.6%), less body weight loss (WMD, 0.51 kg; 95% CI, 0.27 to 0.75). As an add-on intervention with oral antihyperglycemic medication (OAM) and insulin, compared with control (placebo, sitagliptin, exenatide, liraglutide and glargine), dulaglutide lowered HbA1c (WMD, -0.51%; 95% CI, -0.68 to -0.35) and body weight significantly (WMD, -1.30 kg, 95% CI, -1.85 to -1.02) notably, and elicited a similar reduction in FPG (WMD, -0.19 mmol/L; 95% CI, -1.20 to 0.82), an similar incidence of hypoglycemia (24.5% vs. 24.5%). This meta-analysis revealed the use of dulaglutide as a monotherapy or an add-on to OAM and lispro appeared to be effective and safe for adults with T2DM.

Background: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) benefit weight maintenance for diabetic patients. We performed a systematic review to evaluate its weight loss effect on obese/overweight patients without diabetes in randomized controlled trials (RCTs)., Methods: Literature updated to May 5, 2014 from Cochrane Library, MEDLINE, EMBASE and reference lists from relevant articles were identified. RCTs with GLP-1 mimetics treating obese/overweight adults without diabetes for at least 12 weeks were assessed. Studies lacking primary measurements were excluded. Three authors extracted data independently. Either fixed-effect or random-effect models were used to calculate weighted mean differences (WMDs), combined relative risks (RR) and 95% confidence interval (CI) in meta-analyses. Intertrial heterogeneity across studies was examined by I(2) and Q statistics., Results: A total of 1345 individuals retrieved from eight studies were involved and all included trials were of mild-to-moderate bias risks. Participants in GLP-1RA groups achieved a larger weight loss than those in control groups (-2.85 kg, 95%CI -3.55 to -2.14), and liraglutide may work in a dose-dependent fashion. GLP-1RAs also reduced body mass index (BMI) and waist circumferences (WC) and benefited systolic blood pressure and triglyceride regulation. But GLP-1RAs were associated with increased nausea and vomiting events., Conclusions: GLP-1 mimetics induce a weight loss in addition to BMI and WC reduction in obese/overweight adults without diabetes. Further long-term randomized trials and basic studies are required to investigate the mechanisms., (© 2014 Ruijin Hospital, Shanghai Jiaotong University School of Medicine and Wiley Publishing Asia Pty Ltd.)

Introduction: Postprandial hyperglycemia (PPHG) contributes to micro- and macro-vascular complications more than fasting hyperglycemia in patients with type 2 diabetes mellitus. Due to the traditional carbohydrate-rich diet, Asians, particularly Indians and Chinese need agents to control the higher risk of uncontrolled PPHG. Targeting PPHG with α-glucosidase inhibitors (AGIs), either alone or in combination with other oral hypoglycemic agents and insulin, provide overall glycemic control with transient mild gastrointestinal disorders. Treatment with AGIs, especially acarbose, has also shown to provide beneficial effects on lipid levels, blood pressure, coagulation factors, carotid intima-media thickness and endothelial dysfunction. New insights of acarbose therapy obtained like increased activity of gut hormones and improved gut microbiota may explain the benefits on weight, whereas increased production of H2 may explains its cardiovascular benefits to some extent., Areas Covered: A systematic search strategy was developed to identify randomized controlled trials in MEDLINE, PubMed, EMBASE and ongoing trials databases., Expert Opinion: AGIs as a class and acarbose in particular, are most useful in combatting PPHG and glucose variability across the spectrum of diabetes therapy, particularly in Asian patients. Together with their effects on incretin hormones and gut-microbiota AGIs can be considered beyond glycemic control as 'cardio-protective agents.'

Objectives: To evaluate the efficacy and safety of linagliptin in Chinese patients with type 2 diabetes mellitus (T2DM) inadequately controlled by metformin and sulphonylurea., Research Design and Methods: Data for a pre-defined Chinese subgroup who participated in a Phase III randomised, placebo-controlled, 24 week trial (NCT00602472) were analysed. The primary endpoint was change in HbA1c from baseline to 24 weeks. Apart from safety endpoints, secondary endpoints included changes in FPG and measures of insulin secretion and resistance., Results: A total of 192 Chinese patients with T2DM participated in the pre-defined analysis; 144 and 48 patients received linagliptin or placebo, respectively, added to metformin and sulphonylurea. Baseline characteristics (mean [±SD]) for linagliptin and placebo were similar: HbA1c: 8.1% (±0.85) and 8.1% (±0.84); body mass index: 25.9 (±3.2) and 25.6 (±3.4) kg/m², respectively. Placebo-corrected mean (±SE) change in HbA1c from baseline at 24 weeks was -0.68% (0.14) with linagliptin-based treatment (95% CI: -0.96 to -0.39; P<0.0001). Placebo-corrected mean (±SE) change in FPG from baseline at 24 weeks with linagliptin was -18.8 (6.5) mg/dL (-1.0 [0.4] mmol/L; 95% CI: -31.7 to -5.9; P=0.0044). Overall adverse event (AE) rates with linagliptin and placebo including background medication were similar (38.9% and 43.8%, respectively). Drug-related AEs were reported by 12.5% and 2.1% of linagliptin and placebo patients, respectively. Differences were due to hypoglycaemia (10.4% and 0.0%, respectively). No severe hypoglycaemia was reported in either group of this sub-population., Conclusion: Linagliptin in combination with metformin and sulphonylurea has a favourable safety profile and is an efficacious and well tolerated treatment option for Chinese patients with inadequately controlled T2DM. Reduction of sulphonylurea dose should be considered to minimise risk of hypoglycaemia. Although the findings of this pre-specified sub-analysis may be limited by the number of patients in the subgroup, the results were generally consistent with those for the overall population. CLINICALTRIALS IDENTIFIER: NCT00602472.

Background: Because of its mechanism of action, the starch content of a diet might alter the hypoglycemic effect of acarbose., Objective: We aimed to determine whether differences in this hypoglycemic effect existed between individuals consuming Eastern and Western diets with significantly different starch contents, a systematic meta-analysis of studies comparing acarbose with placebo or other hypoglycemic agents in patients with type 2 diabetes mellitus (T2DM) was performed., Methods: Records were retrieved from the Cochrane clinical controlled trials, MEDLINE, EMBASE, Wanfang, Chinese Technical Periodicals, and ongoing trials databases, and full texts and reference lists were screened. Because no study has directly compared patients consuming different types of diet, fixed- and random-effect models were used to indirectly compare the hypoglycemic effect of acarbose monotherapy with that of placebo and/or comparator drugs in patients with T2DM consuming an Eastern (Eastern Asia) or Western (including Europe and North America) diet., Results: A total of 46 studies were included in the meta-analysis. The results revealed that, compared with placebo, hemoglobin A1c (HbA1c) levels were reduced to a significantly greater extent (1.02%) in the Eastern diet (mean [SD], 1.54% [2.00%]) than in the Western diet (mean [SD], 0.52% [1.20%]) P < 0.00001). The ability of acarbose to reduce HbA1c levels in the Eastern (P = 0.20) and Western (P = 0.10) diet groups was similar to that of sulfonylureas, and HbA1c levels were reduced significantly more (0.39%; P < 0.00001) in the Eastern than in the Western diet group. The ability of acarbose to reduce HbA1c levels was similar to those of metformin and nateglinide/repaglinide, but a comparison of its efficacy with different diets was difficult because of the inclusion of few studies in these categories. Analysis of all included studies revealed that acarbose achieved a greater absolute reduction of HbA1c levels in the Eastern diet (mean [SD], 1.26% [1.20%]) than in the Western diet (mean [SD], 0.62% [1.28%]; P < 0.00001) group. However, the poor quality of Eastern diet trials may have affected the outcomes of the meta-analysis., Conclusion: The hypoglycemic effect of acarbose is superior in patients with T2DM consuming an Eastern diet than in those consuming a Western diet and is similar to that of sulfonylureas, metformin, and glinide drugs., (Copyright © 2013 Elsevier HS Journals, Inc. All rights reserved.)

This study aimed to investigate the effect of pioglitazone (PIO) on insulin secretion and mitochondrial ultrastructure and function in 3 cells. HIT-T15 cells were treated with control or palmitate (free fat acids, FFA) or/and PIO and divided into 7 groups: Control group; 0.5 mmol/l FFA (LF); 0.5 mmol/l FFA plus 10-7 mol/I PIO (LFLP); 0.5 mmol/l FFA plus 10-5mol/I PIO (LFHP); 1.0 mmol/l FFA (HF); 1.0 mmol/l FFA plus 10-7mol/I PIO (HFLP); 1.0 mmol/l FFA plus 10-5 mol/I PIO (HFHP). Apoptotic peaks, mitochondrial ultrastructure, ATP/ADP, mRNA levels of peroxisome proliferater activated receptor gamma coactivator-1 (PGC-1) and nucleus respiratory factor-1 (NRF-1) as well as insulin secretion were measured. The results showed that palmitate impaired mitochondrion structure, which could be alleviated by PIO. Palmitate could increase apoptotic peaks, decrease ATP/ADP ratio, enhance the expression of PGC-1 mRNA and NRF-1 mRNA, and decrease glucose stimulated insulin secretion (GSIS). In contrast, PIO could decrease apoptotic peaks, restore partly ATP/ADP ratio, decrease the expression of PGC-1 mRNA and NRF-1 mRNA, and increase GSIS level. These results demonstrate that PIO could ameliorate palmitate induced damage to mitochondrion ultrastructure and function and restore GSIS, accompanied by the modulation of PGC-1 and NRF-1 expression. These findings provide new insight into the hypoglycemic effects of PIO and help develop new agents for diabetes therapy.

The alterations in atherogenic index of plasma (AlP) in type 2 diabetic patients and their normoglycemic first-degree relatives (NFDR) were investigated, and the effects of Acarbose or Glimepiride on AIP in 99 type 2 diabetic patients were evaluated. Triglycerride (TG), total cholesterol, high density lipoprotein-cholesterol (HDL-C) levels were analyzed, and Log (TG/HDL-C) was calculated as AIP in 62 type 2 diabetic patients and their 67 NFDR from 29 type 2 diabetic pedigrees and in 45 healthy controls without family histories of diabetes. Also analyzed were the same parameters in 99 type 2 diabetic patients before and after therapy with Acarbose or Glimepiride. The results revealed that diabetic patients and their NFDR had significantly higher AIP than did the controls, whereas no significant differences were seen between diabetic patients and their NFDR. Positive correlation of AIP between type 2 diabetic patients and their offspring were observed (r = 0.241, P < 0.05). After 8 weeks therapy with Acarbose, the AIP of type 2 diabetic patients was decreased significantly, and no differences were observed for AIP levels in Glimepiride group although the AIP was lower when compared with the untreated level. As a significant inverse correlation of small dense low density lipoprotein (sdLDL) with AIP was confirmed, our data suggest that diabetic patients and their NFDR from type 2 diabetic pedigrees had significantly higher AIP than did controls; AIP could be decreased by therapy with Acarbose in type 2 diabetic patients; Glimepiride may bring potential benefit to type 2 diabetic patients by influencing sdLDL.

Since it is difficult for clinicians to make a decision among the various types of antidiabetic medications due to their great discrepancy in mechanisms, pharmacological properties, and cardiovascular/renal protection, a relatively "precision" or personalized hypoglycemic treatment suggestion is practical for type 2 diabetes (T2D) management in adults. This expert consensus makes some recommendations based on the characteristics of adult T2D patients without clinical cardiovascular disease (CVD) or chronic kidney disease (CKD) by evidence from large‐scale clinical trials. The main consideration for initiating antidiabetic medications is the safety and benefits for prevention of target organ damage, such as CVD and CKD. The choice of personalized glucose‐lowering therapy regarding target organ protection is based on the various effects of antidiabetic medications, patients' clinical characteristics and their key risks, as well as the sociological factors. According to the effects on glucose reduction, cardiovascular protection, renal benefit, body weight change, hypoglycemic risk, and liver function impact, the antidiabetic medications are recategorized in this consensus. Combined with the glucose control target and the different effects of hypoglycemic agents, a significant body of recommendations have been developed for optimal T2D management according to the risk factors for atherosclerotic CVD, heart failure, CKD, primary fatty liver, and hypoglycemia. This consensus gives detailed guidance on personalized antidiabetic therapy initiation in newly diagnosed T2D adults, which attaches great importance to both glucose control and target organ protection. [ABSTRACT FROM AUTHOR]

Patients with type 2 diabetes (T2D) have a higher risk of heart failure (HF) than healthy people, and the prognosis of patients with diabetes and current or previous HF is worse than that of patients with only diabetes. We reviewed the HF outcomes in recently published cardiovascular outcome trials (CVOTs) of three new classes of anti-diabetic agents, namely, dipeptidyl peptidase-4 inhibitors (DPP-4is), glucagon-like-peptide 1 receptor agonists (GLP-1RAs), and sodium glucose cotransporter-2 inhibitors (SGLT-2is) or SGLT-2 and SGLT-1 dual inhibitors and divided the patients into two groups based on the history of HF (with or without) and analyzed their risks of HHF based on the receipt of the aforementioned anti-diabetes drug types. Since the follow-up period differed among the trials, we expressed the rate of HHF as events/1,000 person-years to describe the HF outcome. At last we pooled the data and analyzed their different effects and mechanisms on heart failure outcomes. Although DPP-4is did not increase the risk of HHF in T2D patients with a history of HF, they were associated with a significantly higher risk of HHF among patients without history of HF. Some GLP-1RAs reduced the risk of macrovascular events, but none of these drugs reduced the risk of HHF in patients with T2D irrespective of their HF history. It was not clarified whether SGLT-1/2is can improve the prognosis of macrovascular events in patients with T2D, but these drugs reduced the risk of HHF regardless of patients' histories of HF. This information may be useful or referential for the "precise" selection of hyperglycemic medications. Further researches still needed to clarify the mechanisms of these anti-diabetic medications. [ABSTRACT FROM AUTHOR]

Background. Atherosclerotic cardiovascular disease (ASCVD) is a major cause of death among patients with diabetes but can be improved by certain hypoglycemic agents. However, adjudicating criteria on whether improvements are a glycemic or nonglycemic effect of these agents remain unclear. Methods. Hypoglycemic agents that produce a cardiovascular benefit in nondiabetic patients are considered to do so via a nonglycemic effect. We performed a subgroup analysis for primary and secondary prevention or very high risk of ASCVD in patients with type 2 diabetes (T2DM). Where glycosylated hemoglobin (HbA1c) was reduced to the same extent in a head-to-head comparison, cardiovascular benefits were judged as a nonglycemic effect. Furthermore, by analyzing the endpoints of four important randomized controlled intensive glucose control studies, UKPDS33, ADVANCE, ACCORD, and VADT, we calculated the cut point of HbA1c reduction for a nonglycemic effect on cardiovascular benefit by hypoglycemic agents in ASCVD groups of different severities. Results. For the ASCVD primary prevention group of T2DM, UKPDS33 indicated a reduction in HbA1c < 0.9%, and a cardiovascular benefit within 10 years was considered a nonglycemic effect. For ASCVD secondary prevention or in the very high-risk group, pioglitazone exerted a nonglycemic effect on cardiovascular benefit in nondiabetic patients with insulin resistance; metformin may exert a similar effect in T2DM patients in a head-to-head study. Analysis of T2DM intensive glucose control studies showed a reduction in HbA1c of <1.0%, and a cardiovascular benefit after approximately 5 years was deemed a nonglycemic effect. Conclusions. For ASCVD primary prevention in T2DM, a reduction in HbA1c < 0.9% and a cardiovascular benefit within 10 years were considered a nonglycemic effect. For ASCVD secondary prevention or in a very high-risk population, a reduction in HbA1c < 1.0% and a cardiovascular benefit within about 5 years were also considered a nonglycemic effect. [ABSTRACT FROM AUTHOR]