Analysis of the Endocrine Responses to Anti-Diabetes Drugs: An Issue of Elevated Plasma Renin Concentration in Sodium-Glucose Co-Transporter 2 Inhibitor.

Purpose: Glucose metabolism is associated with several endocrine disorders. Anti-diabetes drugs are crucial in controlling diabetes and its complications; nevertheless, few studies have been carried out involving endocrine function. This study aimed to investigate the association between anti-diabetes drugs and endocrine parameters.

Patients and methods: We performed a study of 180 consecutive patients with type 2 diabetes who attended a medical center. Laboratory measurements of metabolic values and endocrine parameters were assessed after a stable treatment regimen of more than 12 weeks. The differences in various endocrine parameters were compared between subjects with or without certain anti-diabetes drugs, with the administrated anti-diabetes drugs being analyzed to find independent risks associated with elevated endocrine parameters.

Results: After maintaining stable treatment, acceptable glycemic control was noted with an average HbA1c of 7.55% in females and 7.43% in males. Participants taking sulfonylurea (55.8 vs 26.34 ng/L, P=0.043), dipeptidyl peptidase-4 inhibitor (DPP4i) (47.14 vs 32.26 ng/L, P=0.096), or sodium-glucose co-transporter 2 inhibitor (SGLT2i) (64.58 vs 28.11 ng/L, P=0.117) had higher plasma renin concentrations compared to those without this drug but the aldosterone levels did not differ, as well as for other adrenal tests and thyroid function. Under linear regression modeling, SGLT2i was found to be independently associated with a risk of high renin level (beta coefficient: 30.186, 95% confidence interval: 1.71─58.662, P=0.038), whereas sulfonylurea only had borderline associations (B: 21.143, 95% CI: -2.729─45.014, P=0.082). Additionally, renin-angiotensin-aldosterone system (RAAS) blockade (B: 36.728, 95% CI: 12.16─61.295, P=0.004) or diuretics (B: 47.847, 95% CI: 2.039─93.655, P=0.041) was also independently associated with increased renin levels.

Conclusion: SGLT2i was the only class of anti-diabetes drugs independently associated with elevated renin levels, with results similar to RAAS blockade and diuretics. Although SGLT2i appears to protect reno- and cardio-function, the clinical impact of increased renin warrants further precise study for verification.