Metabolic consequences of acute and chronic empagliflozin administration in treatment-naive and metformin pretreated patients with type 2 diabetes

Abstract

Aims/hypothesis Sodium glucose co-transporter 2 (SGLT2) inhibitors lower glycaemia by inducing glycosuria, but raise endogenous glucose production (EGP). Metformin lowers glycaemia mainly by suppressing EGP. We compared the effects of the SGLT2 inhibitor empagliflozin in treatment-naive (TN) and metformin pretreated (Met) patients with type 2 diabetes. Methods A total of 32 TN and 34 patients on a stable dose of metformin, two subgroups of a study that we previously reported, received a mixed meal with double-tracer glucose administration and indirect calorimetry at baseline, after a single 25 mg dose of empagliflozin, and after 4 weeks of treatment with empagliflozin 25 mg/day. Results At baseline, compared with the TN group, the Met group had higher fasting glycaemia (9.1 ± 1.7 vs 8.2 ± 1.3 mmol/l), lower fasting and postmeal insulin secretion, lower beta cell glucose sensitivity (37 [18]

Improving glycaemic control in type 2 diabetes: Stimulate insulin secretion or provide beta‐cell rest?

“…75 Because of other metabolic and haemodynamic effects, the SGLT-2 inhibitor empagliflozin induced a significant reduction in cardiovascular death, hospitalization for heart failure and renal endpoints. [78][79][80] In a head-to-head study with the sulfonylurea glipizide, the SGLT-2 inhibitor dapagliflozin had a lower initial effect on HbA1c reduction (−0.4% vs −0.8%); however, the reduction in glucose levels was more sustained over time with dapagliflozin, resulting in a 0.3% benefit at 208 weeks. Indeed, the SGLT-2 inhibitor dapagliflozin was found not to affect insulin secretion and, paradoxically, increased glucagon secretion from human islets in vitro.…”

“…Indeed, SGLT-2 inhibition was shown to improve various parameters of beta-cell function following a standardized meal test, including beta-cell glucose sensitivity, while actually lowering insulin or C-peptide concentrations, in studies of short duration. [78][79][80] In a head-to-head study with the sulfonylurea glipizide, the SGLT-2 inhibitor dapagliflozin had a lower initial effect on HbA1c reduction (−0.4% vs −0.8%); however, the reduction in glucose levels was more sustained over time with dapagliflozin, resulting in a 0.3% benefit at 208 weeks. 81 agonists attenuate postprandial insulin release.…”

Sodium‐glucose cotransporter 2 inhibitors regulate ketone body metabolism via inter‐organ crosstalk

“…Another noteworthy characteristic of SGLT2i is that they are associated with elevated plasma ketone levels in humans . SGLT2i enhance glucosuria by effectively lowering plasma glucose levels, resulting in decreased fasting insulin and increased fasting glucagon . These hormonal changes cause upregulation of lipolysis in adipose tissue, and also promote a shift in whole‐body substrate utilization from carbohydrate to fat, which mechanistically explains the elevation of ketone bodies in patients treated with SGLT2i .…”

“…[10][11][12] SGLT2i enhance glucosuria by effectively lowering plasma glucose levels, resulting in decreased fasting insulin and increased fasting glucagon. [13][14][15] These hormonal changes cause upregulation of lipolysis in adipose tissue, 12,16 and also promote a shift in whole-body substrate utilization from carbohydrate to fat, which mechanistically explains the elevation of ketone bodies in patients treated with SGLT2i. 14 However, the role of SGLT2i in ketone body metabolism in tissues other than liver is largely unknown.…”

What Are The Benefits In The Association Of SGLT2 Inhibitors And Other Drugs?

“…The SGLT2 inhibitors block the sodium-glucose co-transport type 2, which is responsible for the reabsorption of 90% of the glucose in kidneys, promoting glycosuria and, consequently, the control of type 2 diabetes [1].…”