Initial combination of linagliptin and metformin compared with linagliptin monotherapy in patients with newly diagnosed type 2 diabetes and marked hyperglycaemia: a randomized, double-blind, active-controlled, parallel group, multinational clinical trial.

Aims To evaluate glucose-lowering treatment strategies with linagliptin and metformin in people with newly diagnosed type 2 diabetes and marked hyperglycaemia, a prevalent population for which few dedicated studies of oral antidiabetes drugs have been conducted. Methods A total of 316 patients, with type 2 diabetes diagnosed for ≤12 months and with glycated haemoglobin (HbA1c) concentration in the range 8.5–12.0%, were randomized 1:1 to double-blind, free-combination treatment with linagliptin 5 mg once daily and metformin twice daily (uptitrated to 2000 mg/day maximum) or to linagliptin monotherapy. The primary endpoint was change in HbA1c concentration from baseline at week 24 (per-protocol completers' cohort: n = 245). Results The mean (standard deviation) age and HbA1c at baseline were 48.8 (11.0) years and 9.8 (1.1)%, respectively. At week 24, the mean ± standard error (s.e.) HbA1c decreased from baseline by –2.8 ± 0.1% with linagliptin/metformin and –2.0 ± 0.1% with linagliptin; a treatment difference of –0.8% (95% confidence interval –1.1 to –0.5; p <0.0001). Similar results were observed in a sensitivity analysis based on intent-to-treat principles: adjusted mean ± s.e. changes in HbA1c of –2.7 ± 0.1% and –1.8 ± 0.1%, respectively; treatment difference of –0.9% (95% CI –1.3 to –0.6; p <0.0001). A treatment response of HbA1c <7.0% was achieved by 61 and 40% of patients in the linagliptin/metformin and linagliptin groups, respectively. Few patients experienced drug-related adverse events (8.8 and 5.7% of patients in the linagliptin/metformin and linagliptin groups, respectively). Hypoglycaemia occurred in 1.9 and 3.2% of patients in the linagliptin/metformin and linagliptin groups, respectively (no severe episodes). Body weight decreased significantly with the combination therapy (–1.3 kg between-group difference; p =0.0033). Conclusions Linagliptin in initial combination with metformin in patients with newly diagnosed type 2 diabetes and marked hyperglycaemia, an understudied group, elicited significant improvements in glycaemic control with a low incidence of hypoglycaemia, weight gain or other adverse effects. These results support early combination treatment strategies and suggest that newly diagnosed patients with marked hyperglycaemia may be effectively managed with oral, non-insulin therapy

Linagliptin plus metformin in patients with newly diagnosed type 2 diabetes and marked hyperglycemia

Objectives: Few studies of oral glucose-lowering drugs exist in newly diagnosed type 2 diabetes (T2D) patients with marked hyperglycemia, and insulin is often proposed as initial treatment. We evaluated the oral initial combination of metformin and linagliptin, a dipeptidyl peptidase-4 inhibitor, in this population. Methods: We performed a pre-specified subgroup analysis of a randomized study in which newly diagnosed T2D patients with glycated hemoglobin A1c (HbA1c) 8.5%–12.0% received linagliptin/metformin or linagliptin monotherapy. Subgroups of baseline HbA1c, age, body-mass index (BMI), renal function, race, and ethnicity were evaluated, with efficacy measured by HbA1c change from baseline after 24 weeks. Results: HbA1c reductions from baseline (mean 9.7%) at week 24 in the overall population were an adjusted mean −2.81% ± 0.12% with linagliptin/metformin (n = 132) and −2.02% ± 0.13% with linagliptin (n = 113); treatment difference −0.79% (95% CI −1.13 to −0.46, P < 0.0001). In patients with baseline HbA1c ≥9.5%, HbA1c reduction was −3.37% with linagliptin/metformin (n = 76) and −2.53% with linagliptin (n = 61); difference −0.84% (95% CI −1.32 to −0.35). In those with baseline HbA1c <9.5%, HbA1c reduction was −2.08% with linagliptin/metformin (n = 56) and −1.39% with linagliptin (n = 52); difference −0.69% (95% CI −1.23 to −0.15). Changes in HbA1c and treatment differences between the linagliptin/metformin and linagliptin groups were of similar magnitudes to the overall population across patient subgroups based on age, BMI, renal function, and race. Drug-related adverse events occurred in 8.8% and 5.7% of linagliptin/metformin and linagliptin patients, respectively; no severe hypoglycemia occurred. Conclusion: Linagliptin/metformin combination in newly diagnosed T2D patients with marked hyperglycemia was well tolerated and elicited substantial improvements in glycemic control regardless of baseline HbA1c, age, BMI, renal function, or race. Thus, newly diagnosed, markedly hyperglycemic patients may be effectively treated by combinations of oral agents. Clinical trial registration: www.clinicaltrials.gov identifier is NCT0151297

Initial combination of linagliptin and metformin compared with linagliptin monotherapy in patients with newly diagnosed type 2 diabetes and marked hyperglycaemia: a randomized, double‐blind, active‐controlled, parallel group, multinational clinical trial

Aims To evaluate glucose-lowering treatment strategies with linagliptin and metformin in people with newly diagnosed type 2 diabetes and marked hyperglycaemia, a prevalent population for which few dedicated studies of oral antidiabetes drugs have been conducted. Methods A total of 316 patients, with type 2 diabetes diagnosed for ≤12 months and with glycated haemoglobin (HbA1c) concentration in the range 8.5–12.0%, were randomized 1:1 to double-blind, free-combination treatment with linagliptin 5 mg once daily and metformin twice daily (uptitrated to 2000 mg/day maximum) or to linagliptin monotherapy. The primary endpoint was change in HbA1c concentration from baseline at week 24 (per-protocol completers' cohort: n = 245). Results The mean (standard deviation) age and HbA1c at baseline were 48.8 (11.0) years and 9.8 (1.1)%, respectively. At week 24, the mean ± standard error (s.e.) HbA1c decreased from baseline by –2.8 ± 0.1% with linagliptin/metformin and –2.0 ± 0.1% with linagliptin; a treatment difference of –0.8% (95% confidence interval –1.1 to –0.5; p <0.0001). Similar results were observed in a sensitivity analysis based on intent-to-treat principles: adjusted mean ± s.e. changes in HbA1c of –2.7 ± 0.1% and –1.8 ± 0.1%, respectively; treatment difference of –0.9% (95% CI –1.3 to –0.6; p <0.0001). A treatment response of HbA1c <7.0% was achieved by 61 and 40% of patients in the linagliptin/metformin and linagliptin groups, respectively. Few patients experienced drug-related adverse events (8.8 and 5.7% of patients in the linagliptin/metformin and linagliptin groups, respectively). Hypoglycaemia occurred in 1.9 and 3.2% of patients in the linagliptin/metformin and linagliptin groups, respectively (no severe episodes). Body weight decreased significantly with the combination therapy (–1.3 kg between-group difference; p =0.0033). Conclusions Linagliptin in initial combination with metformin in patients with newly diagnosed type 2 diabetes and marked hyperglycaemia, an understudied group, elicited significant improvements in glycaemic control with a low incidence of hypoglycaemia, weight gain or other adverse effects. These results support early combination treatment strategies and suggest that newly diagnosed patients with marked hyperglycaemia may be effectively managed with oral, non-insulin therapy

Effects of 1 and 3 g cinnamon on gastric emptying, satiety, and postprandial blood glucose, insulin, glucose-dependent insulinotropic polypeptide, glucagon-like peptide 1, and ghrelin concentrations in healthy subjects

BACKGROUND: A previous study of healthy subjects showed that intake of 6 g cinnamon with rice pudding reduced postprandial blood glucose and the gastric emptying rate (GER) without affecting satiety. OBJECTIVE: The objective was to study the effect of 1 and 3 g cinnamon on GER, postprandial blood glucose, plasma concentrations of insulin and incretin hormones [glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1)], the ghrelin response, and satiety in healthy subjects. DESIGN: GER was measured by using real-time ultrasonography after ingestion of rice pudding with and without 1 or 3 g cinnamon. Fifteen healthy subjects were assessed in a crossover trial. RESULTS: The addition of 1 or 3 g cinnamon had no significant effect on GER, satiety, glucose, GIP, or the ghrelin response. The insulin response at 60 min and the area under the curve (AUC) at 120 min were significantly lower after ingestion of rice pudding with 3 g cinnamon (P = 0.05 and P = 0.036, respectively, after Bonferroni correction). The change in GLP-1 response (DeltaAUC) and the change in the maximum concentration (DeltaC(max)) were both significantly higher after ingestion of rice pudding with 3 g cinnamon (P = 0.0082 and P = 0.0138, respectively, after Bonferroni correction). CONCLUSIONS: Ingestion of 3 g cinnamon reduced postprandial serum insulin and increased GLP-1 concentrations without significantly affecting blood glucose, GIP, the ghrelin concentration, satiety, or GER in healthy subjects. The results indicate a relation between the amount of cinnamon consumed and the decrease in insulin concentration