Effect of Dapagliflozin on Insulin Secretion and Insulin Sensitivity in Patients with Prediabetes.

AIM: To evaluate the effect of dapagliflozin on insulin secretion and insulin sensitivity in patients with prediabetes. METHODS: A randomized, double-blind, placebo-controlled clinical trial was carried out in 24 adults diagnosed with prediabetes and without pharmacological treatment. Patients were randomly assigned into two groups of 12 patients each to receive 10 mg of oral dapagliflozin or placebo once a day during 12 weeks. At baseline and at the end of the study, anthropometric and metabolic measurements were evaluated, including the first phase of insulin secretion, total insulin secretion, and insulin sensitivity. RESULTS: After dapagliflozin administration, there were significant decreases in body weight (80.8±16.3 vs. 77.8±14.9 kg, p=0.019), body mass index (30.3±3.5 vs. 29.2±3.1 kg/m2, p=0.023), waist circumference (100.6±13.5 vs. 96.2±11.8 cm, p=0.003), fasting glucose (5.9±0.4 vs. 5.1±0.3 mmol/L, p<0.001) and uric acid (334.3±70.8 vs. 262.9±60.7 mmol/L, p=0.032), with a tendency to increase the insulin sensitivity (1.94±0.72 vs. 2.63±1.04, p=0.064). CONCLUSION: Dapagliflozin administration in patients with prediabetes decreased body weight, body mass index, waist circumference, fasting glucose, and uric acid, with a tendency to increase the insulin sensitivity without changes in insulin secretion.

Effect of dapagliflozin administration on metabolic syndrome, insulin sensitivity, and insulin secretion.

BACKGROUND: The aim of this paper was to evaluate the effect of dapagliflozin on metabolic syndrome (MetS), insulin sensitivity and insulin secretion. METHODS: A randomized, double blind, placebo-controlled clinical trial was carried out in 24 patients with MetS. Glucose and insulin levels were measured every 30 minutes for 2 hours after a 75-g dextrose load. Metabolic profile was also evaluated before and after the pharmacological intervention. Twelve patients received dapagliflozin (10 mg) before breakfast for 90 days. The remaining 12 patients received placebo. Area under the curve (AUC) of glucose and insulin, total insulin secretion, first-phase of insulin secretion and insulin sensitivity were calculated. Data were tested using the Wilcoxon signed-rank, Mann-Whitney U and χ2 tests. The Ethics Committee approved the study protocol. RESULTS: After dapagliflozin, there were significant decreases in body weight (82.8±12.9 vs. 81.2±12.9 kg, P<0.001), BMI (33.4±3.6 vs. 32.7±3.7 kg/m2, P<0.001), waist circumference (102±10 vs. 98±9 cm, P<0.001), total cholesterol (5.4±0.7 vs. 5.2±0.7 mmol/L, P=0.049), triglycerides (2.7±1.4 vs. 1.7±0.8 mmol/L, P=0.003), AUC of insulin (103,914±55,170 vs. 45,018±22,146 pmol/L, P<0.001) and total insulin secretion (0.84±0.64 vs. 0.35±0.11, P<0.001). Seven patients (58.3%) in the dapagliflozin group showed remission of MetS (P=0.027). CONCLUSIONS: Dapagliflozin decreased body weight, BMI, waist circumference, total cholesterol, triglycerides, AUC of insulin and total insulin secretion, with a remission of MetS in 58.3%.

Effect of Ursolic Acid on Metabolic Syndrome, Insulin Sensitivity, and Inflammation.

To evaluate the effect of ursolic acid on metabolic syndrome, insulin sensitivity, and inflammation, a randomized, double-blind, placebo-controlled clinical trial was carried out in 24 patients (30-60 years) with a diagnosis of metabolic syndrome without treatment. They were randomly assigned to two groups of 12 patients, each to receive orally 150 mg of ursolic acid or homologated placebo once a day for 12 weeks. Before and after the intervention, the components of metabolic syndrome, insulin sensitivity (Matsuda index), and inflammation profile (interleukin-6 and C-reactive protein) were evaluated. After ursolic acid administration, the remission of metabolic syndrome occurred in 50% of patients (P = .005) with significant differences in body weight (75.7 ± 11.5 vs. 71 ± 11 kg, P = .002), body mass index (BMI) (29.9 + 3.6 vs. 24.9 ± 1.2 kg/m2, P = .049), waist circumference (93 ± 8.9 vs. 83 + 8.6 cm, P = .008), fasting glucose (6.0 ± 0.5 vs. 4.7 ± 0.4 mmol/L, P = .002), and insulin sensitivity (3.1 ± 1.1 vs. 4.2 ± 1.2, P = .003). Ursolic acid administration leads to transient remission of metabolic syndrome, reducing body weight, BMI, waist circumference and fasting glucose, as well as increasing insulin sensitivity.

Effect of tadalafil administration on insulin secretion and insulin sensitivity in obese men.

AIM: To evaluate the effect of tadalafil administration on insulin secretion and insulin sensitivity in obese men without diabetes. METHODS: A randomized, double-blind, placebo-controlled clinical trial was carried out in obese male patients between 30 and 50 years of age. Eighteen subjects were randomly assigned to two groups of nine patients each. During a 28-day period, subjects received 5 mg orally of tadalafil or placebo each night. Patients were evaluated before and after the intervention. Total insulin secretion and first phase of insulin secretion were calculated by insulinogenic index and Stumvoll index, respectively, and insulin sensitivity was calculated using the Matsuda index. Tolerability and compliance were evaluated permanently throughout the study. RESULTS: There were no significant differences after administration of tadalafil in total insulin secretion (0.82 ± 0.45 vs. 0.61 ± 0.27, p = 0.594), first phase of insulin secretion (1332 ± 487 vs. 1602 ± 800, p = 0.779) and insulin sensitivity (4.6 ± 1.2 vs. 4.9 ± 2.5, p = 0.779). No significant differences were shown in other measurements. CONCLUSION: Tadalafil administration for 28 days did not modify insulin secretion or insulin sensitivity in obese men.