Comparison Between SGLT2 Inhibitors and Lactation: Implications for Cardiometabolic Health in Parous Women

Abstract

Sodium-glucose cotransporter-2 (SGLT2) inhibition and lactation result in the excretion of large amounts of glucose in urine or milk and are associated with a lower risk of cardiovascular events. The respective mechanisms behind this association with cardiovascular protection are not clear. This review compares the contribution of noninsulin-mediated glucose transport during pharmacologic inhibition of SGLT2 with noninsulin-mediated glucose transport during lactation in terms of the implications for the cardiometabolic health of parous women. The search topics used to obtain information on SGLT2 inhibitors included mechanisms of action, atherosclerosis, and heart failure. The search topics used to obtain information on lactation included cardiovascular health and milk composition. Subsequent reference searches of retrieved articles were also used. Active treatment with SGLT2 inhibitors affects glucose and sodium transport in the kidneys and predominantly protects against hospitalization for heart failure soon after the onset of therapy. Active lactation stimulates glucose transport into the mammary gland and improves subclinical and clinical atherosclerotic vascular disease years after delivery. Both SGLT2 inhibitors and lactation have effects on a variety of glucose transporters. Several mechanisms have been proposed to explain the cardiometabolic benefits of SGLT2 inhibition and lactation. Learning from the similarities and differences between both processes will advance our understanding of cardiometabolic health for all people.

Keywords: GLUT1; SGLT2; breastfeeding; cardiovascular; lactation; postpartum.

FIG. 1.

Effect of SGLT2 inhibitors and lactation on the main tissues involved in glucose metabolism. (A) SGLT2 inhibitors induce excretion of 50–100 grams of glucose per day in urine. This drug class promotes a systemic response that mimics starvation despite also inducing hyperphagia. The responses in major metabolic tissues include decreases in hepatic steatosis, visceral and subcutaneous fat, and a mean weight loss of 2–4 kg; and increases in endogenous glucose production (EGP), lipid oxidation, and insulin sensitivity. Insulin secretion improves during hyperglycemic clamps. (B) Active lactation induces excretion of 50–75 grams of glucose per day in milk and is associated with hyperphagia. The responses in major metabolic tissues include decreases in hepatic steatosis, visceral and subcutaneous fat, and increases in EGP. It is unclear how insulin-sensitive are the nonmammary tissues of lactating women. It is not known if glucose uptake in nonmammary tissues is mainly dependent or mainly independent of insulin. Relative to formula-feeding women, insulin secretion decreases during lactation while the amount of secreted insulin for the magnitude of insulin resistance increases.