The Future of Type 2 Diabetes Management: Semaglutide, SGLT2 Inhibitors, and Canagliflozin
1. GLP-1 agonists
GLP-1 receptor agonists (GLP-1RAs) are revolutionizing treatments for type 2 diabetes. Not only do they lower blood sugar levels without leading to weight gain, but studies have even demonstrated improvements in cardiovascular risk factors among those living with Type 2 Diabetes.GLP-1RAs not only offer glycemic control benefits, but they may also slow the progression of chronic kidney disease and nonalcoholic fatty liver disease. This could be attributed to their capacity for reducing inflammation and oxidative stress - both hallmarks of type 2 diabetes.
Multiple studies have suggested that GLP-1RAs may have beneficial effects on microvascular endothelial function in humans with Type 2 Diabetes. These observations are in line with preclinical research demonstrating how activating GLP-1Rs regulates flow-mediated vasodilation of nondiabetic and diabetic mice's arteries.
2. SGLT2 inhibitors
SGLT2 inhibitors are revolutionizing treatments for type 2 diabetes. Not only do they aid with glycemic control, weight loss, and blood pressure reduction, but they have been known to improve heart failure outcomes in those suffering from it by decreasing ejection fraction.SGLT2 inhibitors have a reputation for effectiveness, but their precise physiological effects remain uncertain. We do know they inhibit inflammation and metabolism - though the exact mechanisms remain uncertain.
Clinical trials have focused on the cardiovascular effects of SGLT2 inhibitors, though results are inconsistent. There is evidence that these pharmacological changes are largely due to the direct cardiac actions of these medications.
These direct cardiac effects are due to AMPK and eNOS inhibition, respectively. In most experimental settings, SGLT2i directly reduced inflammation and/or oxidative stress in various cardiac cell types under various pathological conditions such as high-fat diet, hyperglycemia, ischemia/reperfusion, LPS, DOXO, IL-1a/b, TNFa, IL-17a and Ang II.
3. Glucagon-like peptide-1 receptor agonists (GLP-1RAs)
Glycemic control is the key to improving the quality of life for those living with type 2 diabetes. Drug treatment can help achieve and sustain a low glycated hemoglobin (HbA1c) level. The most widely prescribed medication for those affected by diabetes is metformin, a non-insulin drug that reduces glucose production in the liver.
Another medication commonly prescribed for type 2 diabetes is glucagon-like peptide-1 receptor agonists (GLP-1RAs). These drugs work by decreasing glycated hemoglobin levels and decreasing body weight.
However, patients taking GLP-1RAs may have an increased risk of pancreatic cancer. To determine whether this was true, researchers pooled data from observational studies and clinical trials that included type 2 diabetes patients taking a GLP-1RA.On average, 66.7% of patients taking GLP-1RAs also took a long-acting insulin (mean dose, 0.42 +- 0.32 units/kg/d).
By comparison, only 29.6% of those prescribed the drug also received metformin without insulin, while 64.4% received both medications simultaneously.
Tirzepatide is a dual glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptor agonist that has been approved in the US as an add-on treatment for type 2 diabetes patients. Studies have demonstrated its efficacy in improving glycemic control, with potential applications including obesity, nonalcoholic fatty liver disease (NAFLD), and heart failure with preserved ejection fraction (HFpEF).In the SURPASS-3 trial, once-weekly subcutaneous tirzepatide at 5 mg, 10, or 15 mg proved non-inferior and superior to semaglutide 3 mg dose in terms of decreasing glycated hemoglobin levels over 40 weeks. Furthermore, it proved significantly better than placebo for weight reduction.
In the SURMOUNT-1 trial, 2,539 overweight or obese participants with at least one comorbid condition (e.g., hypertension, dyslipidemia, and obstructive sleep apnea) were randomized 1:1:1:1 to either tirzepatide or placebo as an adjunct to a low-calorie diet and increased physical activity. Results showed significant improvements in glycated hemoglobin, body weight, systolic/diastolic blood pressure profiles as well as lipid profiles, and SF-36 physical function scores among these groups.