Effects of insulin glargine versus metformin on glycemic variability, microvascular and beta-cell function in early type 2 diabetes

F Pistrosch,W Landgraf,M Hanefeld,C Köhler,F Schaper,T Forst

doi:10.1007/s00592-012-0451-9

Abstract

We investigated whether basal insulin as first-line treatment in recently diagnosed type 2 diabetes (T2D) can improve glucose control, microvascular function and preserve insulin secretion in comparison with metformin (MET). In this open-label, randomized, prospective 36-week study, 75 patients (44 m, 31 f, mean age 60.7 ± 9.2 year) were allocated to treatment with either MET 1,000 mg b.i.d. (n = 36) or insulin glargine (GLA) at bedtime (n = 39). At baseline and study end, we performed a continuous glucose monitoring for assessment of interstitial glucose (IG) and measured microvascular function using Laser-Doppler fluxmetry. GLA versus MET treatment resulted in a more pronounced reduction in FPG (Δ: 3.1 ± 2.5 vs. 1.4 ± 1.5 mmol/l; p < 0.001) and overall IG (Δ AUC. 671 ± 507 vs. 416 ± 537 mmol/l min; p = 0.04). Postprandial PG and IG differences after a standardized test meal did not reach significance. Proinsulin/C-peptide and HOMA B as marker of endogenous insulin secretion were significantly more improved by GLA. Microvascular blood flow improved only in MET-treated patients. Early basal insulin treatment with GLA in T2D patients provided a better control of FPG, overall IG load and biomarker of beta-cell function compared to the standard treatment with MET. MET treatment resulted in an improvement of microvascular function. Studies of longer duration are needed to evaluate the durability of glucose control and β cell protection with early GLA treatment.

Highlights

Type 2 diabetes mellitus is characterized by an impaired insulin secretion in response to glucose stimulation [1]
We investigated whether basal insulin as firstline treatment in recently diagnosed type 2 diabetes (T2D) can improve glucose control, microvascular function and preserve insulin secretion in comparison with metformin (MET)
Interstitial glucose monitoring demonstrated a more pronounced reduction in mean interstitial glucose (IG) and area under the IG curve (AUC) with insulin glargine, whereas the reduction in the incremental AUC was comparable between treatments (Table 2)

Summary

Introduction

Type 2 diabetes mellitus is characterized by an impaired insulin secretion in response to glucose stimulation [1]. Current treatment guidelines recommend the introduction of metformin at diagnosis in combination with diet and exercise as first-line therapy for type 2 diabetes [4]. Chronic hyperglycemia has harmful effects on glucoseinduced insulin secretion and might accelerate apoptosis of b-cells [7]. Chronic hyperglycemia can deteriorate endothelial function [8]. This glucotoxic effect became apparent if blood glucose concentration exceeds 6.4 mmol/l and is primarily associated with a deterioration of pulsatile insulin secretion and acute insulin response to a

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