SGLT2 Inhibitors and GLP-1s: The Newer Type 2 Diabetes Medications, Explained

SGLT2 inhibitors and GLP-1 medications represent the newest major shift in type 2 diabetes treatment, and both are discussed constantly without always being clearly distinguished from one another. They lower blood sugar through completely different mechanisms, affect weight quite differently, and are not interchangeable despite frequently being mentioned in the same breath.

What These Medications Actually Are

SGLT2 inhibitors and GLP-1 medications are two entirely separate drug classes that both treat type 2 diabetes today, developed and approved years apart, and neither is a newer version of the other despite how often they get lumped together. Both are often added after metformin, though current ADA guidance recommends starting one early, regardless of metformin use or A1C, for people with heart disease, heart failure, chronic kidney disease, or obesity, and both have become genuinely popular partly because they help with weight in a way older diabetes drugs typically did not. The conditions page names both classes as increasingly favored treatment options; this article covers what actually separates them.

An SGLT2 inhibitor is a once-daily oral tablet you swallow. A GLP-1 medication may be oral or, more commonly, a weekly injection, which is part of why the two get confused: patients sometimes describe "the diabetes shot" without knowing which class they actually mean. Both classes have also picked up substantial public attention beyond diabetes specifically, GLP-1 medications especially, which adds another layer of confusion between what a drug is approved for and what it is more broadly known for in the news.

Read More: Type 2 Diabetes: Symptoms, Causes, Diagnosis, Treatment, and Remission

How Each Class Lowers Blood Sugar

SGLT2 inhibitors work in the kidney. They block a protein called SGLT2 that normally reabsorbs glucose back into the bloodstream during filtration, so instead, that glucose passes out in urine rather than being reabsorbed. Less glucose returns to circulation, and blood sugar drops as a direct result, independent of insulin. This is why urinary glucose shows up on testing while taking these medications, an expected effect of how the drug works rather than a sign of a problem. That same sugar in the urine raises the risk of genital yeast infections, and these drugs can cause dehydration and, rarely, a dangerous form of ketoacidosis that can occur even with normal blood sugar, which is why they are usually paused during serious illness or before surgery.

GLP-1 medications work through an entirely different pathway, mimicking a natural hormone released after eating. They stimulate insulin release only when blood sugar is already elevated, reduce glucagon, a hormone that raises blood sugar, and slow how quickly the stomach empties. That last effect is also what drives much of their impact on appetite and weight. Nausea, vomiting, and diarrhea are the most common side effects, especially as doses increase. GLP-1 medications also carry a boxed warning about thyroid C-cell tumors seen in animal studies and should not be used by anyone with a personal or family history of medullary thyroid cancer or MEN2, and severe abdominal pain should be checked promptly for pancreatitis or gallbladder problems.

The Weight Loss Question

This is where the two classes genuinely diverge, though the evidence is more nuanced than the current cultural conversation suggests. Earlier clinical trials found both classes producing roughly similar weight loss, around 2 to 3 kilograms, and at least one retrospective study using older-generation GLP-1 medications found SGLT2 inhibitors outperforming them on weight specifically.

That picture has shifted with newer GLP-1 medications. Current guidance from the American Diabetes Association favors GLP-1 medications specifically when weight loss is a stated treatment goal, and some GLP-1 medications are separately FDA-approved for weight management at higher doses, an approval no SGLT2 inhibitor currently holds. Which specific drug within each class matters more than the class label alone when weight is the deciding factor.

The two classes are not mutually exclusive either. The same research cited above on how GLP-1 medications work also found that adding a GLP-1 medication to an SGLT2 inhibitor improved blood sugar control, weight, and blood pressure beyond the SGLT2 inhibitor alone, without a new safety signal. Combining them is a recognized, studied approach rather than an unusual one.

Is My Diabetes Medication One of These?

Metformin is neither an SGLT2 inhibitor nor a GLP-1 medication, despite being the single most commonly prescribed diabetes drug and often taken alongside either class. Metformin is a biguanide, a different drug family entirely, and works by reducing how much glucose the liver produces rather than by acting on the kidney or mimicking a gut hormone. The three classes are frequently combined precisely because they work through unrelated mechanisms rather than competing for the same pathway, which is also why side effects and monitoring differ meaningfully between them despite all three treating the same underlying condition.

• Brenzavvy (bexagliflozin), an SGLT2 inhibitor FDA-approved in 2023, is effective on its own or combined with metformin; like other SGLT2 inhibitors, it is not used in type 1 diabetes

Where to Start

If weight loss is a specific goal alongside blood sugar control, say so explicitly when discussing options, since that stated priority can reasonably point toward a GLP-1 medication over an SGLT2 inhibitor even when both would control blood sugar adequately on their own. If heart failure or kidney disease is part of the picture, mention that too, since SGLT2 inhibitors carry particular benefits there that are worth weighing carefully alongside whatever else is being considered.

Neither class is always a first prescription, though guidance increasingly starts one early for people with heart, kidney, or weight-related goals, so if one is being suggested, it is worth asking plainly and directly what changed: whether metformin alone stopped being enough, a new health consideration emerged, or a specific goal like weight loss is now part of the plan. That context shapes which of the two classes, or a combination of both, actually fits best for the situation at hand.

Read More: Type 2 Diabetes: Symptoms, Causes, Diagnosis, Treatment, and Remission