Effect of linagliptin on glucose metabolism and pancreatic beta cell function in patients with persistent prediabetes after metformin and lifestyle.

The goal of the study was to evaluate the effect of adding linagliptin to metformin and lifestyle on glucose levels and pancreatic ß-cell function in patients with persistent impaired glucose tolerance (IGT) after 12 months of metformin and lifestyle. A single center parallel double-blind randomized clinical trial with 6 months of follow-up was performed in patients with persistent IGT after 12 months of treatment with metformin and lifestyle; patients were randomized to continue with metformin 850 mg twice daily (M group, n = 12) or linagliptin/metformin 2.5/850 mg twice daily (LM group, n = 19). Anthropometric measurements were obtained by standard methods and by bioelectrical impedance; glucose was measured by dry chemistry, insulin by chemiluminescence, and pancreatic ß-cell function was calculated with the disposition index using glucose and insulin values during oral glucose tolerance test (OGTT) and adjusting by insulin sensitivity. The main outcomes were glucose levels during OGTT and pancreatic ß-cell function. Patients in the LM group had a reduction in weight (-1.7 ± 0.6, p < 0.05) and body mass index (BMI, -0.67 ± 0.2, p < 0.05). Glucose levels significantly improved in LM group with a greater reduction in the area under the glucose curve during OGTT (AUCGluc0_120min) as compared to the M group (-4425 ± 871 vs -1116 ± 1104 mg/dl/120 min, p < 0.001). Pancreatic ß-cell function measured with the disposition index, improved only in LM group (2.3 ± 0.23 vs 1.7 ± 0.27, p 0.001); these improvements persisted after controlling for OGTT glucose levels. The differences in pancreatic ß-cell function persisted also after pairing groups for basal AUCGluc0_120min. The addition of linagliptin to patients with persistent IGT after 12 months of treatment with metformin and lifestyle, improved glucose levels during OGTT and pancreatic ß-cell function after 6 months of treatment.Trial registration: Clinicaltrials.gov with the ID number NCT04088461.

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

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 ß-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 ß-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 ±â€¯6 and 18 ±â€¯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 ß-cell function, and reduced T2D incidence in subjects with prediabetes as compared to metformin and lifestyle.