The combination of linagliptin, metformin and lifestyle modification to prevent type 2 diabetes (PRELLIM). A randomized clinical trial

Metabolism. 2020 Mar:104:154054. doi: 10.1016/j.metabol.2019.154054. Epub 2019 Dec 28.

Abstract

Background: Prediabetes is a highly prevalent health problem with a high risk of complications and progression to type 2 diabetes (T2D). The goals of this study were to evaluate the effect of the combination of lingaliptin + metformin + lifestyle on glucose tolerance, pancreatic β-cell function and T2D incidence in patients with prediabetes.

Methods: A single center parallel double-blind randomized clinical trial with 24 months of follow-up in patients with impaired glucose tolerance plus two T2D risk factors which were randomized to linagliptin 5 mg + metformin 1700 mg daily + lifestyle (LM group) or metformin 1700 mg daily + lifestyle (M group). Primary outcomes were regression to normoglycemia and T2D incidence; glucose levels and pancreatic β-cell function were secondary outcomes.

Results: Subjects were screened for eligibility by OGTT and 144 patients with prediabetes were randomized to LM group (n = 74) or M group (n = 70); 52 and 36 participants in the LM group and 52 and 27 participants in the M group, completed the 12 and 24 months of treatment, respectively; average follow-up was 17 ± 6 and 18 ± 7 months in M and LM group, respectively. Glucose levels during OGTT improved more in LM group. OGTT disposition index (DI) improved significantly better during the first months in LM group, increasing from 1·31 (95% CI: 1·14-1·49) to 2·41 (95% CI: 2.10-2.72) and to 2.07 (95% CI: 1.82-2.31) at 6 and 24 months in LM group vs from 1.21 (95% CI: 0.98-1.34) to 1.56 (95% CI: 1.17-1.95) and to 1.72 (95% CI: 1.45-1.98) at 6 and 24 months in M group (p < .05). T2D incidence was higher in M group in comparison to LM group (HR 4.0, 95% CI: 1.24-13.04, p = .020). The probability of achieving normoglycemia was higher in LM group (OR 3.26 CI 95% 1.55-6.84). No major side effects were observed during the study.

Conclusions: The combination of linagliptin, metformin and lifestyle improved significantly glucose metabolism and pancreatic β-cell function, and reduced T2D incidence in subjects with prediabetes as compared to metformin and lifestyle.

Keywords: Linagliptin; Metformin; Prediabetes; Type 2 diabetes prevention.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Blood Glucose / metabolism
  • Combined Modality Therapy
  • Diabetes Mellitus, Type 2 / drug therapy
  • Diabetes Mellitus, Type 2 / prevention & control*
  • Double-Blind Method
  • Female
  • Follow-Up Studies
  • Glucose Intolerance / drug therapy
  • Glucose Intolerance / therapy
  • Glucose Tolerance Test
  • Humans
  • Hypoglycemic Agents / therapeutic use*
  • Insulin-Secreting Cells / metabolism
  • Life Style*
  • Linagliptin / therapeutic use*
  • Male
  • Metformin / therapeutic use*
  • Middle Aged
  • Treatment Outcome

Substances

  • Blood Glucose
  • Hypoglycemic Agents
  • Linagliptin
  • Metformin