Abstract
BackgroundDipeptidyl peptidase 4 (DPP4) inhibitors improve glycemic control by promoting GLP1-mediated glucose-dependent insulin secretion and suppression of glucagon. Sitagliptin and vildagliptin have been shown to improve insulin sensitivity in patients with type 2 diabetes mellitus (T2DM). However, these patients had uncontrolled blood glucose at inclusion; therefore, the improvement in insulin sensitivity observed in these studies could be attributed to the drug per se and/or reduction in glucotoxicity. This study examines the effect of linagliptin on insulin sensitivity and β-cell function in patients with well-controlled T2DM.MethodsThirty patients with T2DM of duration ≤5 years, and having HbA1c < 7.5% were randomized to receive linagliptin, voglibose or placebo (n = 10 each), and were followed up for 6 months. Insulin sensitivity was assessed by hyperinsulinemic-euglycemic clamp, and insulin secretory response was measured by basal (M0) and postprandial (M1) β-cell function, and area under curve (AUC) for C-peptide during mixed meal tolerance test.ResultsThe median HbA1c of the study subjects at inclusion was 6.9% and there was no significant difference among the groups in terms of age, duration of diabetes, body mass index (BMI), HbA1c, insulin sensitivity, AUC of C-peptide and M0 and M1 at baseline. At the end of the study, there was a modest reduction in HbA1c (− 0.2%) in the linagliptin group, and a significant decrease (− 0.8%) in the voglibose group, as compared to placebo (p = 0.038). However, there were no significant differences in insulin sensitivity, M0 and M1 and AUC of C-peptide, within, or among the groups.ConclusionLinagliptin modestly improves glycemic profile in patients with well controlled T2DM; however, it may not have an effect on insulin sensitivity in these patients.Trial registrationRetrospectively Registered in Clinicaltrials.gov (ID number, NCT02097342). Registered: March 27, 2014.
Highlights
Dipeptidyl peptidase 4 (DPP4) inhibitors improve glycemic control by promoting Glucagon-like peptide-1 (GLP1)-mediated glucose-dependent insulin secretion and suppression of glucagon
A plethora of drugs are available for the treatment of type 2 diabetes mellitus (T2DM); incretin-based therapies such as dipeptidyl peptidase-4(DPP-4) inhibitors and glucagon like peptide-1(GLP-1) receptor agonists are among the recent additions to the therapeutic armamentarium in T2DM [2]
After 6 months of linagliptin and voglibose therapy reduced the glycated hemoglobin (HbA1c) from 6.8 to 6.6% (p = 0.474) and 7.0 to 6.6%; p = 0.015), respectively, whereas in the control group, HbA1c did not change (Table 2, Fig. 2)
Summary
Dipeptidyl peptidase 4 (DPP4) inhibitors improve glycemic control by promoting GLP1-mediated glucose-dependent insulin secretion and suppression of glucagon. Sitagliptin and vildagliptin have been shown to improve insulin sensitivity in patients with type 2 diabetes mellitus (T2DM) These patients had uncontrolled blood glucose at inclusion; the improvement in insulin sensitivity observed in these studies could be attributed to the drug per se and/or reduction in glucotoxicity. Few studies have reported an improvement in insulin sensitivity with DPP-4 inhibitors, sitagliptin and vildagliptin [9, 10] These studies included patients with uncontrolled diabetes (HbA1c > 8%) and one of the potential reasons for the improvement in insulin sensitivity observed in these studies could be due to reduction in glucotoxicity, rather than the direct effect of these drugs on peripheral utilization of glucose. Linagliptin has been shown to improve insulin sensitivity in diet-induced obese mice [11]
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