Efficacy and Safety of Sitagliptin in Hispanic/Latino Patients with Type 2 Diabetes: A Pooled Analysis from Ten Randomized, Placebo-Controlled Phase 3 Clinical Trials

Abstract

IntroductionTo assess the efficacy and safety profile of the dipeptidyl-peptidase-4 inhibitor sitagliptin in a population of self-identified Hispanic/Latino patients with type 2 diabetes.MethodsData were pooled from ten randomized, double-blind studies in which subjects were treated with sitagliptin 100 mg/day (as mono- or combination therapy) or placebo, and used to evaluate the glycemic efficacy, safety, and tolerability of sitagliptin compared with placebo after 24 weeks of treatment.ResultsA total of 804 Hispanic/Latino patients were included in the analysis. Baseline characteristics in the treatment groups were similar (mean baseline HbA1c of approximately 8.5%). The LS mean HbA1c changes from baseline were − 0.94% with sitagliptin and − 0.32% with placebo, and the between-group difference was − 0.62%, p < 0.001. After 24 weeks of treatment, 35% and 18% of subjects were at the HbA1c goal of < 7% in the sitagliptin and placebo groups, respectively. Body weight increased slightly in both treatment groups. Incidences of adverse events of hypoglycemia were similar and low (1.9% and 1.4% for sitagliptin and placebo, respectively) in both groups in studies in which insulin or sulfonylurea were not used and were similar (9% and 11% for sitagliptin and placebo, respectively) when all studies were included. Overall safety and tolerability of treatment with sitagliptin and placebo were similar. No clinically meaningful differences between the safety profile of sitagliptin in the Hispanic/Latino population analyzed here and broader populations previously evaluated were observed.ConclusionIn this pooled analysis of sitagliptin therapy vs placebo in Hispanic/Latino patients, sitagliptin provided significant improvement in glycemic control and was generally well tolerated.FundingMerck & Co., Inc., Kenilworth, NJ, USA.

Dipeptidyl peptidase IV inhibition delays developmental programming of obesity and metabolic disease in male offspring of obese mothers

“…Expanding on the role of glucose, DPPIV inhibitors such as sitagliptin are effective against T2DM [11][12][13]15 . Sitagliptin improved glycemic control in randomized controlled clinical trials involving adults with T2DM, indicated by a 20% reduction in hemoglobin A1C [22][23][24][25][26][27] ; this protective effect has been attributed to decreased degradation of the incretin hormones GLP-1 and GIP, both of which potentiate glycemic control after a meal and promote satiety, acting over time to improve metabolic function 62 . However, the effects of sitagliptin on weight control remain unclear.…”

“…In mice, greater plasma DPPIV activity is observed in models of genetic obesity (ob/ob) and diet-induced obesity (DIO) 20 ; meanwhile, mice that lack one or both Dpp4 alleles in adipocytes and/or hepatocytes exhibit reduced plasma DPPIV activity and are protected from DIO 21 . DPPIV has also been extensively studied in the context of T2DM and insulin signaling, and DPPIV inhibitors such as sitagliptin are effective, United States Food and Drug Administration (FDA)-approved second-line treatments for T2DM [22][23][24][25][26][27] . In line with the hypothesis that DPPIV is an active player in obesity progression, results from clinical trials indicate that DPPIV inhibitors can improve weight control [28][29][30][31][32][33][34] , systemic metabolism [22][23][24][25][26][27] , and inflammatory responses [35][36][37][38][39][40][41][42][43] all critical processes that become progressively dysregulated in the context of obesity.…”

“…DPPIV has also been extensively studied in the context of T2DM and insulin signaling, and DPPIV inhibitors such as sitagliptin are effective, United States Food and Drug Administration (FDA)-approved second-line treatments for T2DM [22][23][24][25][26][27] . In line with the hypothesis that DPPIV is an active player in obesity progression, results from clinical trials indicate that DPPIV inhibitors can improve weight control [28][29][30][31][32][33][34] , systemic metabolism [22][23][24][25][26][27] , and inflammatory responses [35][36][37][38][39][40][41][42][43] all critical processes that become progressively dysregulated in the context of obesity. Nonetheless, despite extensive research efforts, the precise role of DPPIV in obesity progression remains to be determined.…”

Effects and Safety of Sitagliptin in Non-Alcoholic Fatty Liver Disease: A Systematic Review and Meta-Analysis

“…Both of the abovementioned studies indicated that sitagliptin has no effect on improving liver fibrosis. Additionally, most of the included studies demonstrated no improvement in hepatic content, possibly because sitagliptin has only slight effects on weight loss [59,61].…”