New Medications for Diabetes: More Than Just Blood Sugar
The Bottom Line: New classes of antidiabetic medications have demonstrated effects beyond reducing blood glucose, including reducing weight, lowering the risk of cardiovascular events, decreasing heart failure hospitalizations, and slowing the progression of kidney disease.
New Antidiabetic Medications
Two new classes of antidiabetic medications have been associated with substantial benefits beyond blood glucose lowering: glucagon-like peptide-1 (GLP1) receptor agonists and sodium-glucose cotransporter 2 (SGLT2) inhibitors.
GLP1 receptor agonists: These medications are related to gastrointestinal hormones that augment the natural response to nutrient intake by slowing gastric emptying, stimulating insulin production and inhibiting the release of glucagon. These effects result in a reduction in blood glucose with a corresponding low risk of hypoglycemia, and a feeling of fullness with reduced appetite. These medications are currently available only in injectable formulations, although oral formulations are in development. Examples include:
● semaglutide (OzempicⓇ, WegovyⓇ, RybelsusⓇ)
● liraglutide (VictozaⓇ, SaxendaⓇ, XultophⓇ)
● dulaglutide (TrulicityⓇ)
● tirzepatide (MounjaroⓇ)
SGLT2 inhibitors: These medications increase the urinary excretion of glucose with greater effects at higher blood glucose levels, thereby lowering blood glucose without risk of hypoglycemia. This results in a mild diuretic effect, a small reduction in blood pressure, as well as a small caloric loss. Examples include:
● canagliflozin (InvokanaⓇ)
● dapagliflozin (ForxigaⓇ, XigduoⓇ, various generics)
● empagliflozin (JardianceⓇ, SynjardyⓇ)
Beneficial Effects Beyond Blood Glucose Reduction
Weight Loss: The use of both GLP1 receptor agonists and SGLT2 inhibitors can lead to weight loss, although the effect is much greater with the former. This has led to increasing use of GLP1 receptor agonists as weight loss therapy for patients with and without diabetes.
Reduced Cardiovascular Events: GLP1 receptor agonists have demonstrated a consistent reduction in major adverse cardiovascular events (myocardial infarction, nonfatal stroke, or cardiovascular death) and all-cause mortality. The reduction in cardiovascular events and death has even been demonstrated in patients with diabetes, and in those with pre-existing cardiovascular disease and overweight but without diabetes.
Reduced Hospitalization for Heart Failure: SGLT2 inhibitors have demonstrated a consistent reduction in heart failure hospitalizations and heart failure mortality in patients with and without diabetes. This also includes patients with a left ventricular ejection fraction greater than 40%, representing one of the few therapies with proven benefits in this group.
Renal Protection: SGLT2 inhibitors have demonstrated a protective effect on renal function. These agents slow the progression of kidney disease at all stages, and can significantly delay the development of end-stage kidney disease.
Diabetes Canada Guideline Recommendations
Diabetes Canada recommends the use of GLP1 receptor agonists either in addition to, or in place of, metformin in patients with diabetes and a diagnosis of atherosclerotic cardiovascular disease (ASCVD), and in those over 60 years old with cardiovascular risk factors including tobacco use, dyslipidemia, or hypertension (Grade A recommendation).
SGLT2 inhibitors are recommended in patients with diabetes and established ASCVD, heart failure, or chronic kidney disease (Grade A recommendation).
Key Points:
● Two new classes of antidiabetic medications, GLP1 receptor agonists and SGLT2 inhibitors, have shown substantial benefits beyond blood glucose lowering
● GLP1 receptor agonists produce significant weight loss and a reduction in major cardiovascular events and death
● SGLT2 inhibitors significantly reduce the risk of heart failure hospitalizations and death, and slow the progression of chronic kidney disease
References:
Am Fam Physician 2024;109(4):333-342.
Atherosclerosis 2024:394:117560.
Can J Diabetes 2018;42(Suppl 1):S1-S325.
