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Initial short-term intensive insulin therapy as a strategy for evaluating the preservation of beta-cell function with

R Retnakaran1, Y Qi, C Opsteen

  • 1Leadership Sinai Centre for Diabetes, Mount Sinai Hospital, Toronto, Ontario, Canada. rretnakaran@mtsinai.on.ca

Diabetes, Obesity & Metabolism
|October 6, 2010
PubMed
Abstract

Insights

Intensive insulin therapy (IIT) helped assess oral antidiabetic drugs (OADs) like sitagliptin. However, sitagliptin did not significantly preserve beta-cell function in type 2 diabetes mellitus (T2DM) despite improving A1c.

Area of Science:

  • Endocrinology
  • Metabolic Diseases
  • Pharmacology

Background:

  • Type 2 diabetes mellitus (T2DM) management is challenged by accurately assessing beta-cell function due to hyperglycemia's confounding effects (glucotoxicity).
  • Intensive insulin therapy (IIT) can normalize glucose levels, potentially allowing for a clearer evaluation of drug effects on beta-cells.
  • This strategy was employed to investigate the impact of sitagliptin on beta-cell function, independent of glucotoxicity.

Purpose of the Study:

  • To evaluate the beta-cell protective capacity of sitagliptin in patients with type 2 diabetes mellitus.
  • To utilize a novel approach employing short-term intensive insulin therapy (IIT) to mitigate glucotoxicity and assess oral antidiabetic drug (OAD) effects.
  • To determine if sitagliptin preserves beta-cell function in T2DM patients after an IIT-induced euglycemic period.

Main Methods:

  • A pilot study involving 37 T2DM patients (duration 6.0 ± 6.4 years, A1c 7.0 ± 0.8%) initially on 0-2 OADs.
  • Patients underwent 4-8 weeks of IIT (basal detemir, premeal insulin aspart), followed by randomization to metformin with sitagliptin (n=10) or placebo (n=11) for 48 weeks.
  • Beta-cell function was assessed using the ratio of the area under the curve of C-peptide to glucose (AUC(Cpep/gluc)) adjusted for HOMA-IR.

Main Results:

  • Sitagliptin treatment led to higher fasting glucagon-like-peptide-1 levels and lower A1c compared to placebo.
  • While beta-cell function initially improved during IIT, it declined similarly in both sitagliptin and placebo groups over the 48-week follow-up.
  • No significant difference in beta-cell function (AUC(Cpep/gluc)/HOMA-IR) was observed between the sitagliptin and placebo arms by the study's end.

Conclusions:

  • Short-term IIT is a viable strategy for assessing the beta-cell protective effects of diabetes interventions.
  • Despite improving glycemic control (A1c), sitagliptin did not demonstrate a significant protective effect on beta-cell function in this pilot study.
  • The confounding influence of glucotoxicity on beta-cell function assessment in T2DM can be mitigated using a pretreatment IIT approach.

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