Context: Sodium-glucose cotransporter 2 (SGLT2) inhibitors induce glycosuria and improve glycemic control, β cell function and insulin sensitivity in type 2 diabetes mellitus (DM2). On the other hand, these drugs predispose to diabetic ketoacidosis by increasing the tonus of glucagon. Glucagon acts on the liver and has no relevant effect on peripheral lipolysis and release of free fatty acids (FFA) as a substrate for ketogenesis, an action attributed to growth hormone (GH). This study aimed to evaluate the role of GH in promoting FFA disposal for ketogenesis in pre-diabetic or DM2 patients treated with empagliflozin 25mg daily.
Design and methods: Seventeen individuals were included in the study. They were all over 18 years old, both sexes, with pre-diabetes or DM2 without use of any antidiabetic drug, excepted metformin; body mass index between 25 and 40 kg/m2 and HbA1c >5.7 and <11%. Exclusion criteria were: presence of microalbuminuria or chronic renal disease, pregnancy, previous bariatric surgery, liver or heart disease that has repercussion on glycemic control and uncontrolled thyroid dysfunction. After an overnight fast, the participants were submitted to tests where blood samples were obtained at the times: −60, 0, 30, 60, 90, 120, 180, 240 minutes. At time −60 was administrated placebo (test 1) or empagliflozin 25 mg (test 2 and 3). All individuals ate a standard meal (1 boiled egg, parmesan cheese 50 g and bread 125 g) at time 0. After the test 1, all subjects were instructed to take empagliflozin 25 mg daily and the same procedure was done on day 21(test 2) and 28 (test 3). Thirty-six hours before the test 3, all subjects received pegvisomant 30 mg subcutaneous. Plasma concentrations of insulin, glucose, triglycerides, glucagon, GH, total cholesterol and fractions, FFA and IGF-1 were measured.
Result: When we compared to placebo (test 1), the treatment with empagliflozin diminished the plasma levels of glucose (−15.1, −16.7%, P < 0.05), insulin (−20.0, −23.3% P < 0.05), insulin/glucagon ratio (−21.6, −32.0%, P < 0.05) and FFA (−20.3, −23.4%, P < 0.05); and also increased the plasma glucagon levels (7.9, 10.7%, P < 0.05) - for test 2 and test 3 vs test 1, respectively for all. As expected, the plasma GH concentrations did not alter between test 1 and test 2, but increased dramatically at test 3 (3885%).
Conclusion: Blocking the effect of GH with pegvisomant did not alter the plasma concentrations of FFA in pre-diabetes or DM2 patients treated with empagliflozin.
18 - 21 May 2019
European Society of Endocrinology