Obesity is more than a metabolic disorder—it’s a complex condition that can severely impact quality of life and increase the risk of serious health complications, even premature death. Over the past 50 years, obesity has reached epidemic levels worldwide. While many strategies are available to manage it, clinical research has shown that certain diabetes drugs can aid in weight loss.
These medications are often prescribed off-label—meaning they’re used for purposes not officially approved by the FDA—but they still provide valuable benefits. Each drug works differently, targeting processes like appetite control or energy expenditure to help reduce weight.
9 Diabetic Drugs For Weight Loss
Below is an overview of several diabetes medications known to promote weight loss, along with their effectiveness and potential side effects.
Active ingredients: Tirzepatide
Drug class: GIP/GLP-1 receptor agonist
Dosage form: Pen and vial
Dosage frequency: Once a week
Common side effects: Nausea, diarrhea, decreased appetite, vomiting, constipation, indigestion, and abdominal pain.
Pros:
Cons:
Mounjaro demonstrated significant, dose-dependent weight reductions in participants across all trials. Key observations include:
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- SURPASS-1 trial: Participants experienced average weight reductions of 14 to 20.94 lbs. In contrast, those on the placebo only saw a reduction of 2 lbs.
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- SURPASS-2 trial: At 40 weeks, mean reductions in body weight were approximately 16.76 to 25 lbs with Mounjaro, compared to 13 lbs with semaglutide.
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- SURPASS-3 trial: At week 52, the three Mounjaro doses decreased body weight by approximately 16.53 lbs to 28.44 lbs. In contrast, those receiving insulin degludec experienced a weight gain of 5.07 lbs.
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- SURPASS-5 trial: In a 40-week study, the average weight reductions from the participants’ initial weights were 12 lbs to 19 lbs, while individuals on the placebo showed an average weight gain of 4 lbs.
Tirzepatide, the active ingredient in Mounjaro, was also studied in a separate set of trials (SURMOUNT trials) to evaluate its effectiveness as a weight-loss treatment. It later received FDA approval for chronic weight management in obese or overweight adults and is now marketed under the brand name Zepbound.
Active ingredients: Semaglutide
Drug class: GLP-1 receptor agonist
Dosage form: Pen
Dosage frequency: Once a week
Common side effects: Nausea, vomiting, diarrhea, abdominal pain and constipation.
Pros:
Cons:
The extent of Ozempic’s weight reduction effects varied across different studies within the SUSTAIN program. For example:
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- SUSTAIN-3 trial: Participants receiving Ozempic experienced an average weight loss of 12.3 lbs, compared to 4.2 lbs with exenatide extended-release.
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- SUSTAIN-7 trial: Ozempic resulted in an average weight loss of 10.1 to 14.3 lbs. In comparison, dulaglutide groups saw weight losses of 5.1 to 6.6 lbs.
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- SUSTAIN-10 trial: Participants treated with Ozempic lost an average of 12.8 lbs, whereas those receiving liraglutide lost 4.2 lbs.
Similar to Mounjaro, the active ingredient in Ozempic was also studied for weight management. The formulation, approved in 2017, is marketed under the brand name Wegovy and is currently indicated for individuals aged 12 and older with obesity.
Active ingredients: Liraglutide
Drug class: GLP-1 receptor agonist
Dosage form: Pen
Dosage frequency: Once a day
Common side effects: Nausea, diarrhea, vomiting, decreased appetite, dyspepsia, constipation, and immunogenicity-related events, including urticaria.
Pros:
Cons:
In clinical studies ranging from 26 to 52 weeks in length, many participants lost weight. For instance, when Victoza was added to metformin, participants lost an average of up to 6.2 lbs. Another study found that switching from sitagliptin to liraglutide resulted in additional weight loss, with participants losing up to 5.51 lbs.
Another version of liraglutide that is FDA-approved for weight loss is also available under the brand name Saxenda.
Active ingredients: Dulaglutide
Drug class: GLP-1 receptor agonist
Dosage form: Pen
Dosage frequency: Once a week
Common side effects: Nausea, diarrhea, vomiting, abdominal pain, and decreased appetite.
Pros:
Cons:
In a 52-week study evaluating the efficacy of Trulicity, participants experienced varying levels of weight loss depending on the dosage. Those taking Trulicity 1.5 mg had an average weight loss of 6.7 lbs, while those on the 0.75 mg dose lost an average of 5.7 lbs. In comparison, participants receiving the comparator, sitagliptin, lost 3.4 lbs.
Active ingredients: Semaglutide
Drug class: GLP-1 receptor agonist
Dosage form: Tablets
Dosage frequency: Once a day
Common side effects: Nausea, abdominal pain, diarrhea, decreased appetite, vomiting, and constipation.
Pros:
Cons:
The PIONEER clinical trials evaluated the efficacy of Rybelsus, with weight loss as a secondary outcome. The biggest weight loss reported occurred in the PIONEER-2 trial, where participants taking the 14 mg dose of Rybelsus experienced an average weight loss of 10.4 lbs over 26 weeks.
This was followed closely by PIONEER-4, where participants on the same dose lost 9.7 lbs, compared to 6.8 lbs in the liraglutide group and 2.6 lbs in the placebo group.
6. Metformin (Glucophage and Glumetza)
Active ingredients: Metformin
Drug class: Biguanide
Dosage form: Tablets
Dosage frequency: Immediate-release metformin is usually taken 2-3 times a day, while the extended-release version is taken once daily.
Common side effects: Nausea, diarrhea, stomach upset or cramping, bloating, gas, loss of appetite, metallic taste in the mouth, and a risk of vitamin B12 deficiency.
Pros:
Cons:
An older study examined how effective metformin is for treating obesity in people without type 2 diabetes. Over 6 months, those treated with metformin lost an average of 12.8 lbs, while untreated patients gained 1.8 lbs. Later studies found more promising results, such as increased expression of genes related to brown adipose tissue (BAT) activity, energy expenditure, and fat metabolism.
Active ingredients: Empagliflozin
Drug class: SGLT-2 inhibitor
Dosage form: Tablets
Dosage frequency: Once a day
Common side effects: Urinary tract infections, increased urination, genital infections (e.g., yeast infections), dehydration, low blood pressure, and increased cholesterol levels.
Pros:
Cons:
Jardiance has shown clinically meaningful effects on weight loss. In a pooled analysis of four 24-week studies, Jardiance reduced body weight by 4.19 lbs compared to placebo. Additionally, a retrospective trial compared the weight-loss effects of empagliflozin and liraglutide. After one year, the empagliflozin group achieved an average weight loss of 6.2 lbs, while the liraglutide group lost 4.8 lbs.
Active ingredients: Dapagliflozin
Drug class: SGLT-2 inhibitor
Dosage form: Tablets
Dosage frequency: Once a day
Common side effects: Genital yeast infections, urinary tract infections, infections like a cold or flu, increased urination, constipation, back pain, nausea, and increased cholesterol levels.
Pros:
Cons:
A 2020 study showed that participants in the dapagliflozin group experienced an average weight loss of 2.4 lbs, a BMI reduction of 0.3 kg/m², and a decreased waist circumference of 0.9 inches.
Another trial found that dapagliflozin reduced epicardial fat thickness and led to an average weight loss of 7.7 lbs. Epicardial fat, a type of visceral fat, surrounds the heart and coronary arteries. While it serves protective functions, excessive epicardial fat is strongly linked to obesity, insulin resistance, and type 2 diabetes.
Active ingredients: Canagliflozin
Drug class: SGLT-2 inhibitor
Dosage form: Tablets
Dosage frequency: Once a day
Common side effects: Vaginal and penile yeast infections, increased urination, and nocturia (increased need to urinate at night).
Pros:
Cons:
A systematic review and meta-analysis found that canagliflozin significantly reduced weight by an average of 7.3 lbs, with similar effects observed at both the 100 mg and 300 mg doses. In another study, canagliflozin demonstrated greater weight loss compared to liraglutide (7.7 lbs vs. 4.2 lbs).
Takeaway
Several diabetes medications offer the added benefit of weight loss, linked to their influence on specific molecular pathways. Among these, Mounjaro, a newer medication for type 2 diabetes, delivered the most significant weight-loss effects, even outperforming Ozempic. However, more studies are needed to confirm its long-term safety and effectiveness.
Understanding how these medications interact with existing health conditions or other treatments will also be critical. Consulting a healthcare provider is the best approach when starting a medication to support weight loss. They can assess your medical history, current health status, and goals to recommend a safe and effective treatment plan.
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