In individuals with type 2 diabetes, SGLT2-inhibitors increase beta-cell glucose sensitivity (BGS) and insulin sensitivity. This effect has been attributed to glucotoxicity alleviation; however, few research has taken into account changes in glycemia. The effects of empagliflozin on BGS and secondarily, peripheral insulin sensitivity (IS), compared to similar glycemic control with insulin treatment were explored.

17 subjects with T2D were treated with empagliflozin and NPH-insulin for 5 weeks in a randomized cross-over study design with a 3-week of washout period included. Insulin doses were adjusted to achieve equivalent glycemic control as empagliflozin.

Both the treatments similarly reduced glycaemia and fasting insulin concentrations were lower with empagliflozin and higher with insulin. Empagliflozin resulted an increase in fasting hepatic glucose production compared to insulin, but postprandial hepatic glucose production did not differ between treatments. Beta-cell glucose sensitivity was greater with empagliflozin compared to insulin and insulin sensitivity was found to be unchanged with empagliflozin, but it decreased with insulin compared to washout. Fatty tissue insulin resistance was lower with empagliflozin compared to insulin.

Reduced glucotoxicity does not result in improved beta-cell function with empagliflozin treatment. Insulin resistance can be caused by peripheral hyperinsulinemia.

Within the EMPRISE® monitoring program, the cardiovascular effectiveness of empagliflozin (EMPA) vs. glucagon-like peptide-1 receptor agonists (GLP1RA) or liraglutide were evaluated. The patients ≥18 years with type 2 diabetes initiating (i) EMPA vs. GLP1-RA or (ii) EMPA vs. liraglutide were identified. Primary outcomes were hospitalization for heart failure (HHF), myocardial infarction (MI), stroke, and all-cause mortality.

Relative to GLP1RA, EMPA had a lower risk of hospitalization for heart failure, and a similar risk of myocardial infarction, stroke, and mortality. Patients with and without CVD had similar outcomes. Estimates from EMPA vs. liraglutide, both overall and across subgroups, were similar to those from GLP1 RA.

When compared to GLP-1RA or liraglutide, EMPA was linked with a lower risk of hospitalization for heart failure but a similar risk of myocardial infarction, stroke, and death throughout the CVD spectrum in real-world patients.

EMPRISE is a 5-year monitoring program that uses Medicare and two commercial claims in the United States to assess the efficacy and safety of empagliflozin (EMPA). A total of 190,226 type 2 diabetes patients aged 18 years or older who started EMPA or a dipeptidyl peptidase-4 inhibitor (DPP-4i) and were followed for heart failure hospitalization in primary or any discharge position a composite of MI and stroke, and all-cause mortality (ACM). Safety outcomes were lower-limb amputations (LLA), non-vertebral fractures, diabetic ketoacidosis (DKA), acute kidney injury (AKI), renal and bladder cancers.

EMPA was linked to a lower risk of hospitalization for heart failure, a similar risk of MI or stroke, and a lower risk of all-cause mortality when compared to DPP4i. EMPA was associated with lower risk of acute kidney injury, higher risk of diabetic ketoacidosis, and a similar risk of lower-limb amputations, fractures, and renal and bladder cancer.

In conclusion, these findings back up EMPA's cardiovascular effectiveness in normal treatment, with a safety profile that matches recorded data.