The world of type 2 diabetes has seen a massive revolution in the last decade. From improved technologies such as continuous glucose monitoring devices (CGM), to improved GLP-1 receptor agonists, to the expansion of SGLT2 inhibitors---insulin is quickly becoming an antiquated tool in our tool belt.

CGM devices, once reserved for patients with type 1 diabetes or those on intensive insulin regimens, are now increasingly recommended for individuals with type 2 diabetes. Evidence from randomized clinical trials and meta-analyses demonstrates that CGM use in adults with type 2 diabetes—whether on insulin, GLP-1 RA, or oral agents—results in significant reductions in HbA1c compared to blood glucose monitoring. This is due to the accountability that is provided, when patients learn how various foods, stressors and physical activities impact their glucose levels. These sensors are all compatible with smart phone apps which allow for easy connectivity to their doctors. Commonly used sensors include the FreeStyle Libre 2 Plus and Libre 3 Plus (15-day wear time) as well as the Dexcom G6 and Dexcom G7 (10-day wear time). Medicare will now pay for a CGM device for any type 2 diabetic on at least 1 insulin injection per day. We hope that eventually Medicare will cover CGM devices for all diabetics regardless of insulin usage given the tremendous benefits. Recent guidelines from the American Diabetes Association and the American Association of Clinical Endocrinology recommend offering CGM to all patients with type 2 diabetes on insulin, and considering it for those on non-insulin therapies, with a goal of achieving >70% time in range (70–180 mg/dL). In addition, there is strong evidence that shows a significantly reduced risk of hypoglycemia and death from hypoglycemia in insulin dependent patients.

SGLT2 inhibitors are now recognized as a transformative therapy for cardiovascular risk reduction. These agents, including empagliflozin, canagliflozin, dapagliflozin, and ertugliflozin (common name brands include Jardiance and Farxiga), act by promoting renal glucose excretion, but their benefits extend far beyond glycemic control. Cardiovascular outcome trials have consistently demonstrated that SGLT2 inhibitors reduce major adverse cardiovascular events (MACE), cardiovascular death, and heart failure hospitalizations. In the EMPA-REG OUTCOME trial, empagliflozin reduced MACE by 14% and cardiovascular death by 38% in patients with established cardiovascular disease. The CANVAS study showed similar reductions in MACE and heart failure hospitalization with canagliflozin, while DECLARE-TIMI 58 demonstrated a significant reduction in cardiovascular death or heart failure hospitalization with dapagliflozin, even in patients without preexisting cardiovascular disease. Meta-analyses confirm these findings: SGLT2 inhibitors reduce MACE (hazard ratio [HR] ~0.90), all-cause mortality (HR ~0.86), and heart failure hospitalization (HR ~0.69) compared to placebo or other glucose-lowering drugs. These benefits are observed across diverse populations, including those with heart failure (both reduced and preserved ejection fraction), chronic kidney disease, and varying degrees of cardiovascular risk. The cardiovascular benefits of SGLT2 inhibitors are rapid and robust, with reductions in heart failure events seen within weeks of initiation. The magnitude of heart failure risk reduction (27–35%) is among the largest of any glucose-lowering therapy. Importantly, these effects are independent of baseline glycemic control, and SGLT2 inhibitors are now recommended for patients with type 2 diabetes and established atherosclerotic cardiovascular disease, heart failure, or chronic kidney disease, regardless of HbA1c. SGLT2 inhibitors also confer renal protection, lowering the risk of progression to end-stage kidney disease and cardiovascular or renal death. The safety profile is favorable, with the most common adverse events being mild genital infections and a small increased risk of diabetic ketoacidosis, which can be mitigated with patient education.

GLP-1 RAs have become a cornerstone of type 2 diabetes management, with robust evidence supporting their efficacy in lowering HbA1c, promoting weight loss, and reducing cardiovascular and renal risk.These agents augment glucose-dependent insulin secretion, suppress glucagon, slow gastric emptying, and reduce appetite, leading to improved glycemic and metabolic profiles. Currently the 2 most widely used agents include semaglutide (known as Ozempic), and tirzepatide, a dual GLP-1/GIP agonist (known as Mounjaro). Tirzepatide has demonstrated superior reductions in HbA1c (2–2.5%) and weight (11–13%) compared to semaglutide and placebo, and is now approved for weight management and obstructive sleep apnea in adults with obesity. Incidentally, when indicated by the FDA for obesity management, semaglutide is known as Wegovy and tirzepatide is known as Zepbound. Semaglutide is also indicated for the treatment of noncirrhotic metabolic dysfunction-associated steatohepatitis (MASH), formerly known as nonalcoholic steatohepatitis (NASH), with moderate to advanced liver fibrosis (consistent with stages F2 to F3 fibrosis) in adults.

GLP-1 RAs are recommended as the preferred first injectable therapy for type 2 diabetes, even before insulin initiation, due to their efficacy and safety profile. They are particularly indicated for patients with established cardiovascular disease, multiple cardiovascular risk factors, or chronic kidney disease, with specific agents (dulaglutide, liraglutide, semaglutide) approved for reducing major adverse cardiovascular events and renal outcomes. They are generally well tolerated, with gastrointestinal side effects (nausea, vomiting, diarrhea) being the most common and typically transient, and mitigated by improved hydration, and dietary protein intake. GLP-1 RAs continue to evolve, with new indications, formulations, and combination therapies on the horizon.

Given the wide array of indications for GLP-1 and SGLT2 inhibitor therapies, we have now adopted a multidisciplinary team approach to the care of our patients with T2DM and metabolic syndrome, which includes primary care physicians, nephrologists, cardiologists, hepatologists, sleep medicine physicians, endocrinologist and more.

Despite so many new classes of medications for type 2 diabetes, metformin still continues to show great benefit in reducing the risk of diabetic complications, over the decades, and has stood the test of time. Endocrinologists are generally reserving sulfonylureas and insulin as a last resort after the use of the above agents, due to the risk of hypoglycemia and lack of cardiovascular benefit.

However cost concerns remain the biggest barriers to use of these new classes of medications. There are some options for cash-discount pricing. For example, an SGLT2 inhibitor known as Brenzavvy (Bexagliflozin) is available online at CostPlus Drugs for $49.85 per month, which represents considerable savings for patients. In response to congressional and public pressure, Novo Nordisk recently reduced the cash price of Ozempic from >$1000 per month to $499 per month, though the average price in Europe ranges from $59-$103 per month. Ultimately, it will certainly require physician advocacy to ensure that these invaluable, life-saving tools can be accessed by all of our patients with type 2 diabetes, regardless of income status.

Dr. Pallavy (Polly) Reddy, MD, FACE, is a CMA member, PLA Alumni, and a Board Certified Endocrinologist at the Diabetes and Endocrinology Center of Ohio (DECO).