Metabolism: clinical and experimental | 2019

The combination of Linagliptin, Metformin and Lifestyle Modification to prevent Type 2 Diabetes (PRELLIM). A randomized clinical trial.



BACKGROUND\nPrediabetes 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.\n\n\nMETHODS\nA single center parallel double-blind randomized clinical trial with 24\u202fmonths of follow-up in patients with impaired glucose tolerance plus two T2D risk factors which were randomized to linagliptin 5\u202fmg\u202f+\u202fmetformin 1700\u202fmg daily + lifestyle (LM group) or metformin 1700\u202fmg daily + lifestyle (M group). Primary outcomes were regression to normoglycemia and T2D incidence; glucose levels and pancreatic β-cell function were secondary outcomes.\n\n\nRESULTS\nSubjects were screened for eligibility by OGTT and 144 patients with prediabetes were randomized to LM group (n\u202f=\u202f74) or M group (n\u202f=\u202f70); 52 and 36 participants in the LM group and 52 and 27 participants in the M group, completed the 12 and 24\u202fmonths of treatment, respectively; average follow-up was 17\u202f±\u202f6 and 18\u202f±\u202f7\u202fmonths 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\u202fmonths 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\u202fmonths in M group (p\u202f<\u202f.05). T2D incidence was higher in M group in comparison to LM group (HR 4.0, 95% CI: 1.24-13.04, p\u202f=\u202f.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.\n\n\nCONCLUSIONS\nThe 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.

Volume None
Pages \n 154054\n
DOI 10.1016/j.metabol.2019.154054
Language English
Journal Metabolism: clinical and experimental

Full Text