β-Cell-Relieving Effects of Basal Insulin Plus Metformin (MET) Treatment in Type 2 Diabetes (T2D) Patients (Pts) Using Insulin Glargine (GLA) or NPH Insulin (NPH)
Abstract Number: 448-P
Authors: CLOTH HOHBERG, MARTIN LARBIG, ANDREAS PFÜTZNER, WERNER ROTH, THOMAS FORST
Institutions: Mainz, Germany, Berlin, Germany
Results: Postprandial (pp) release of intact proinsulin is a marker of β-cell dysfunction in pts with T2D. This parallel, two-arm, pilot study tested the β-cell-relieving effect of a basal insulin-optimized treatment (BOT) by combining MET with either NPH or GLA. 28 insulin-naïve T2D pts (mean±SD age, 61.5±6.7 yr; T2D duration, 9.8±6.5 yr; A1c, 7.1±0.5%; BMI, 30.7±4.3 kg/m2) were randomized to BOT with MET plus either NPH or GLA at bedtime (both titrated to FBG <100 mg/dL). At baseline and after 3 months of treatment, pts received a standardized breakfast, lunch and dinner, with subsequent preprandial and pp blood sampling (60 and 120 min) for the measurement of intact proinsulin, total insulin and blood glucose values. Insulin dose after 3 months was comparable in both treatment groups (NPH 23.3±12.7 vs GLA 23.6±13.4 IU; p=NS). Both treatments reduced fasting glucose levels (NPH 157±34 to 119±29 mg/dL; GLA 158±19 to 121±22 mg/dL; p<0.01 vs baseline, respectively). No difference was observed in fasting or pp glucose levels between treatment groups. A powerful reduction of overall intact proinsulin levels was observed in both treatment arms (table). While the pp release of intact proinsulin after breakfast did not differ between treatments, GLA led to a stronger reduction in pp intact proinsulin release after lunch and dinner. By contrast, total plasma insulin levels, representing endogenous and exogenous insulin resources, did not differ between treatment groups. Basal insulin supplementation, in addition to MET treatment, effectively reduces pp β-cell load. While NPH and GLA evolve comparable effects at breakfast, GLA relieves β-cell stress more effectively at dinner and by trend at lunch. Despite comparable glucose control, the prolonged pharmacodynamic profile of GLA results in stronger β-cell effects, lasting >24 hr.
2-hr pp area under the curve for intact proinsulin