SGLT-2 Inhibitors vs GLP-1 Medications for Weight Loss

Looking to manage weight effectively? Here's a quick breakdown:

• SGLT-2 Inhibitors: Promote modest weight loss (1.5–3 kg) by increasing glucose excretion through urine. Ideal for individuals with type 2 diabetes and cardiovascular or kidney concerns.
• GLP-1 Medications: Deliver more significant weight loss (up to 15–17.8%) by reducing appetite and slowing digestion. Best for those focused on weight management.
• Combination Therapy: Combining both can enhance weight loss results (5.7 kg sustained over a year).

Quick Comparison

Both options have unique benefits and risks. Consult your healthcare provider to choose what fits your health needs and goals.

SGLT2 Inhibitors vs GLP-1 Agonists: Expert Comparison

How These Medications Work

SGLT-2 Inhibitors: How They Affect Glucose in the Kidneys

SGLT-2 inhibitors work by blocking the reabsorption of glucose in the kidneys, causing your body to remove about 60–100 grams of glucose through urine each day ^[5]. This process, called glucosuria, naturally reduces calorie intake.

Since this method doesn’t rely on insulin, it triggers several metabolic changes:

"SGLT2 inhibitors help your kidneys remove the extra glucose (sugar) and sodium (salt) from your body through the urine (pee) to keep a healthy balance in your blood." – National Kidney Foundation ^[4]

Over time, the body may compensate with a 10–15% boost in calorie intake, which can limit weight loss ^[3]. While SGLT-2 inhibitors primarily depend on calorie reduction, other medications focus on reducing appetite.

GLP-1 Medications: Tackling Appetite Directly

Unlike SGLT-2 inhibitors, GLP-1 medications address hunger and digestion. These drugs mimic the GLP-1 hormone produced in the small intestine ^[1], helping you feel full by:

• Enhancing satiety signals
• Slowing how quickly the stomach empties
• Regulating insulin and glucagon levels

This approach directly targets overeating, complementing the calorie-reducing effects of SGLT-2 inhibitors ^[1].

When used together, these medications may work even better. GLP-1 drugs can help offset the increased calorie intake sometimes seen with SGLT-2 inhibitors, potentially leading to more effective weight management ^[3].

Weight Loss Results

SGLT-2 Inhibitors: Weight Loss Data

Clinical trials show that SGLT-2 inhibitors lead to moderate and steady weight loss. On average, patients lose about 3 kg over 52 weeks, with nearly 2 kg shed in the first 6 months ^[7].

When paired with other diabetes treatments, the weight loss results vary:

GLP-1 Medications: Weight Loss Data

GLP-1 medications, on the other hand, deliver more pronounced weight loss. In the STEP 1 trial, semaglutide resulted in a 14.9% drop in body weight over 68 weeks, compared to a 2.4% reduction in the placebo group ^[2]. Additional research highlights:

For users of Wegovy (semaglutide), weight loss typically progresses as follows:

• 4% reduction after 2 months
• 6% after 3 months
• 8% after 4 months
• 15% after 17 months ^[8]

These trends highlight the differences between the two drug classes.

Results Comparison

GLP-1 medications consistently outperform SGLT-2 inhibitors in terms of weight loss. For instance, 86.4% of semaglutide users achieved at least a 5% reduction in body weight, compared to 31.5% in the placebo group ^[2].

"Patients should be aware of side effects, how to manage the side effects, [and] when to consider stopping the medication if they have side effects. They should also make sure that there is good follow up and accountability with the provider with whom they are working and that there isn't just a plan for weight loss but also for maintenance."
– Janelle Duah, MD, Assistant Professor of Medicine at Yale School of Medicine ^[6]

The mechanisms behind these results differ: SGLT-2 inhibitors promote calorie loss through glucosuria, while GLP-1 medications reduce appetite, leading to more substantial weight loss. SGLT-2 inhibitors tend to cause early weight loss ^[3], whereas GLP-1 medications show significant initial reductions that often level off after six months ^[7]. Interestingly, combining both has shown encouraging outcomes, with sustained weight loss of 5.7 kg maintained over a year in obese individuals without diabetes ^[3].

sbb-itb-b172b91

Side Effects and Safety

SGLT-2 Inhibitors: Common Side Effects

SGLT-2 inhibitors work by increasing glucose excretion through urine, which can lead to specific side effects. Common issues include genital yeast infections (thrush), frequent urination, back pain, dizziness, and mild rashes. However, more serious risks include diabetic ketoacidosis (DKA), severe dehydration, urinary tract infections (UTIs), Fournier's gangrene, and a higher likelihood of bone fractures ^[10].

GLP-1 Medications: Common Side Effects

GLP-1 medications primarily affect the digestive system, with up to half of patients experiencing gastrointestinal symptoms ^[12]. Common side effects include nausea, vomiting, diarrhea, and constipation. More severe complications can involve pancreatitis, gastroparesis, or bowel obstruction. Rapid weight loss associated with these medications may also result in facial sagging (often called "Ozempic face") and gallstone formation.

Both SGLT-2 inhibitors and GLP-1 medications require close monitoring, which will be discussed further.

Safety Overview

The safety profiles of these medications vary due to their different mechanisms of action. For SGLT-2 inhibitors, clinical guidelines recommend stopping their use before surgery, during extended fasting, or in critical illness to reduce the risk of DKA ^[13].

Key Safety Considerations:

SGLT-2 Inhibitors – Avoid Use In:

• Individuals with type 1 diabetes
• Patients with an estimated glomerular filtration rate below 60 mL/min ^[11]
• Those with hematuria or a history of bladder cancer ^[13]
• Immunocompromised kidney transplant recipients ^[13]

GLP-1 Medications – Use Caution In:

• Pregnant individuals (contraindicated)
• Patients with a history of pancreatitis
• Those with gastroparesis
• Individuals with prior bowel obstructions ^[9]

For patients using GLP-1 medications, eating smaller meals slowly and avoiding intense physical activity after eating can help minimize gastrointestinal discomfort ^[9]. Both medication types require regular check-ins with healthcare providers to ensure safety. The choice between them often depends on a person's specific health conditions, risks, and lifestyle.

Selecting the Right Medication

Key Decision Points

When deciding between SGLT-2 inhibitors and GLP-1 medications, it's important to consider individual health needs and treatment objectives. Here's a quick comparison:

For patients with cardiovascular disease (but no chronic kidney disease), SGLT-2 inhibitors have been shown to lower overall mortality rates (NNT=39 over five years) ^[15]. On the other hand, newer GLP-1 therapies like Tirzepatide are achieving better weight loss results compared to medications such as Semaglutide ^[14]. These decisions should always be made under medical supervision to ensure the best outcomes.

Medical Guidance Requirements

When starting SGLT-2 inhibitors, renal function should be monitored within the first three months. For GLP-1 medications, begin with a low dose and increase gradually to minimize gastrointestinal discomfort. Regular follow-ups are critical for both types of medications to evaluate their effectiveness and address any side effects.

Combining SGLT-2 inhibitors with appetite-suppressing agents may improve weight loss results ^[3]. Additionally, combination therapy can provide extra benefits for patients dealing with atherosclerotic cardiovascular disease, heart failure, or kidney conditions ^[3].

Online Treatment Options

Remote treatment options are now more accessible than ever. For example, Join Layla offers GLP-1 treatment plans, including medications like Semaglutide and Tirzepatide, starting at $197 per month for Compounded Semaglutide. Their service includes evaluations by licensed providers, customized treatment plans, medication delivery, and ongoing clinical support - all without requiring insurance.

While telehealth simplifies access to GLP-1 treatments, SGLT-2 inhibitors often need closer in-person monitoring due to their effects on kidney function and cardiovascular health ^[15]. Cost differences are also notable - GLP-1 receptor agonists are generally two to three times more expensive than SGLT-2 inhibitors ^[15].

Conclusion

Main Points Review

SGLT-2 inhibitors work by increasing glucose excretion, leading to modest weight loss of about 1.5–2 kg. On the other hand, GLP-1 medications reduce appetite and slow down gastric emptying, resulting in more noticeable weight loss of 2–4 kg ^[3]. Among these, newer GLP-1 drugs have shown particularly strong results. For example, Tirzepatide - a dual GIP and GLP-1 receptor agonist - has delivered better weight loss outcomes compared to medications like Semaglutide ^[14].

This comparison highlights the strengths of each option, helping you weigh the pros and cons.

Getting Started

Now that you have the facts, it’s time to decide which treatment aligns with your health needs. If cardiovascular or kidney health is a priority, SGLT-2 inhibitors may be the way to go. If weight loss is your main focus, GLP-1 medications might be a better fit. Reviewing the data with your healthcare provider can help you choose between the broader benefits of SGLT-2 inhibitors and the targeted weight-loss effects of GLP-1 drugs.

For those interested in GLP-1 treatments, telehealth platforms like Join Layla offer convenient options, including provider consultations, medication delivery, and ongoing support. Always make treatment decisions under medical guidance, considering your health goals, potential side effects, and overall medical history.