Jardiance vs Mounjaro 2026: SGLT2 vs Dual GIP/GLP-1 Comparison Guide

Jardiance (empagliflozin), an SGLT2 inhibitor, and Mounjaro (tirzepatide), a dual GIP/GLP-1 receptor agonist, represent two fundamentally different approaches to treating type 2 diabetes. According to the EMPA-REG OUTCOME trial published in the New England Journal of Medicine, Jardiance achieved a 38% reduction in cardiovascular mortality in patients with established heart disease. Meanwhile, the SURPASS-2 trial demonstrated Mounjaro’s superior glycemic control with up to 2.3% A1C reduction and significant weight loss of up to 12.4 kg (approximately 27 lbs).

This comprehensive guide compares these diabetes medications across efficacy, side effects, cost, and patient selection criteria for 2026, helping you and your doctor determine which treatment best fits your medical history and health goals.

TL;DR: Jardiance vs Mounjaro Quick Summary

Jardiance (empagliflozin) and Mounjaro (tirzepatide) are both FDA-approved for type 2 diabetes but serve different primary purposes. Choose Jardiance if you have heart failure, chronic kidney disease, or established cardiovascular disease—it reduces CV death by 38% (EMPA-REG trial) and costs approximately $629/month. Choose Mounjaro if significant weight loss is your priority—it delivers up to 21% body weight reduction and 2.3% A1C improvement but costs around $1,080/month. Jardiance is a daily pill with UTI/yeast infection risks; Mounjaro is a weekly injection with GI side effects. Neither is approved for type 1 diabetes.

Mechanism: SGLT2 vs GIP/GLP-1 Action

While both these medications lower blood sugar levels, their mechanisms target completely different physiological pathways.

Jardiance (Empagliflozin)

Jardiance is an SGLT2 (sodium-glucose cotransporter 2) inhibitor that works by blocking glucose reabsorption in the kidneys. According to the FDA prescribing information, this active ingredient (empagliflozin) causes the kidneys to excrete 50-90 grams of extra glucose daily through urine, creating a caloric deficit of 200-300 calories. This mechanism also promotes osmotic diuresis, which helps lower blood pressure by approximately 4/2 mmHg and reduces fluid retention—providing direct kidney benefits and kidney protection for patients with chronic kidney disease.

Jardiance is an oral tablet (daily pill) available in 10 mg and 25 mg doses, taken once daily with or without food. It’s approved for adults and pediatric patients aged 10 years and older with type 2 diabetes, as well as for heart failure and chronic kidney disease treatment regardless of diabetes status.

Mounjaro (Tirzepatide)

Mounjaro contains tirzepatide, a dual glucose-dependent insulinotropic polypeptide (GIP) and GLP-1 receptor agonist. Per the Mounjaro prescribing information from Eli Lilly, this novel medication slows gastric emptying by approximately 40%, suppresses appetite, and increases insulin secretion in a glucose-dependent manner. The dual-action approach targets both incretin hormone receptors, potentially doubling the postprandial insulin response while promoting weight loss through reduced food intake and increased satiety.

Mounjaro is administered as a once weekly injection in the abdomen, thigh, or upper arm. The dosage starts at 2.5 mg and can be titrated up to a maximum of 15 mg. It helps the pancreas make more insulin to lower blood glucose while simultaneously reducing body weight and appetite.

Key Difference: Jardiance works metabolically through kidney glucose excretion and diuresis; Mounjaro works hormonally through appetite suppression, delayed gastric emptying, and enhanced insulin secretion.

Efficacy Comparison Table

Clinical trials provide the most reliable evidence for comparing jardiance vs mounjaro effectiveness. The table below summarizes key outcomes from landmark studies including EMPA-REG OUTCOME, SURPASS-2, and the EMPEROR trials.

Summary: Mounjaro dominates in glycemic control and weight loss metrics, while Jardiance has unmatched cardiovascular and renal endpoints with proven outcomes data.

Jardiance vs Mounjaro Weight Loss

When comparing jardiance vs mounjaro weight loss outcomes, Mounjaro demonstrates substantially greater effectiveness. In the SURPASS-2 trial, patients treated with Mounjaro 15mg achieved approximately 21% body weight reduction (average of 12.4 kg or 27 lbs), compared to Jardiance’s more modest 3-5% weight loss (3-4 kg) that typically plateaus around month 6.

The weight loss mechanisms differ significantly. Jardiance promotes weight loss primarily through caloric loss via increased urination (allowing excess sugar to be excreted), with initial weight loss of 2-3 kg often representing water weight. Mounjaro, however, directly reduces appetite and slows gastric emptying, leading to reduced food intake and more significant weight loss that targets visceral fat (up to 40% reduction in some studies).

For patients where losing weight is a primary goal alongside blood sugar control, Mounjaro offers a clear advantage. Some clinical trials suggest combination therapy with both SGLT2 inhibitors and GLP-1 agonists may provide up to 27% total weight loss, though this approach requires careful medical supervision.

Side Effects Comparison

Both diabetes medications can cause serious side effects, but their profiles differ substantially. Understanding these common adverse reactions helps patients and doctors make informed decisions.

Both medications can increase the risk of low blood sugar when taken with insulin or sulfonylureas. Jardiance has fewer gastrointestinal side effects compared to Mounjaro, while Mounjaro may reduce the efficacy of oral hormonal contraceptives due to delayed gastric emptying.

Cost Comparison 2026

There are significant differences in monthly expenses:

Medicare typically covers Jardiance for type 2 diabetes, heart failure and chronic kidney disease, while Mounjaro coverage for diabetes is increasingly available but may require prior authorization. Patients can reduce costs using prescription coupons from platforms like GoodRx or SingleCare.

Jardiance vs Mounjaro Heart Failure

The EMPEROR-Reduced trial demonstrated that Jardiance reduced the combined risk of cardiovascular death or hospitalization for heart failure by 25% in patients with heart failure with reduced ejection fraction (HFrEF).

Jardiance is FDA approved to reduce the risk of cardiovascular death in adults with type 2 diabetes and established heart disease. The EMPEROR-Preserved trial made history as the first successful trial for heart failure with preserved ejection fraction (HFpEF), a condition previously considered untreatable. 

Jardiance can help reduce blood pressure, which provides added heart benefits and kidney protection. The SURPASS-CVOT trial for Mounjaro cardiovascular outcomes is ongoing, with data expected by 2029.

Dosing & Administration Guide

Jardiance Schedule

Jardiance is a daily pill taken once daily, with or without food. The starting dose is typically 10 mg, which may be increased to 25 mg if additional glycemic control is needed. No dosage adjustment is required based on kidney problems for most patients, though it may be less effective for blood sugar lowering in severe kidney disease (eGFR below 30 mL/min/1.73m²). The medication can be taken at any time of day.

Mounjaro Titration

Mounjaro is administered as a once weekly injection subcutaneously in the abdomen, thigh, or upper arm. The dosage starts at 2.5 mg for the first 4 weeks, then increases in a step-wise approach: 5 mg → 7.5 mg → 10 mg → 12.5 mg → 15 mg (maximum). Each dose level is maintained for at least 4 weeks before increasing. Injection sites should be rotated with each dose. The medication can be taken at any time of day, with or without food.

Patient Selection: Jardiance vs Mounjaro

Choose Jardiance if you have: 

Heart failure or established cardiovascular disease, chronic kidney disease (eGFR 20-90), need for kidney protection, blood pressure concerns, cost sensitivity, or are an elderly patient. Avoid Jardiance if: You have recurrent urinary tract infections or genital yeast infections, or are prone to dehydration.

Choose Mounjaro if: 

Significant weight loss is a priority, you have BMI >35 with obesity as a major concern, A1C >9% requiring aggressive glycemic control, or you are a younger patient without cardiovascular disease. Avoid Mounjaro if: You have gastroparesis, history of thyroid cancer (especially medullary thyroid cancer), Multiple Endocrine Neoplasia syndrome type 2 (MEN 2), or cannot tolerate gastrointestinal side effects.

Combination Therapy: For patients with established cardiovascular disease AND obesity, combination therapy with both medications may provide optimal benefits—up to 1.8% additional A1C reduction and 25% weight loss. However, this approach requires careful monitoring by your doctor and consideration of your complete medical history.

Important: Neither Mounjaro nor Jardiance is approved for type 1 diabetes. Both medications can be combined with other diabetes drugs but have different risk profiles. Mounjaro is linked to risks during pregnancy, including potential adverse effects on the fetus. Consult your doctor before starting either medication.

EMPA-REG vs SURPASS Clinical Trial Data

EMPA-REG OUTCOME (n=7,020): This landmark cardiovascular outcomes trial, published in The New England Journal of Medicine, randomized patients with type 2 diabetes and established cardiovascular disease to Jardiance or placebo. Results showed a 38% relative risk reduction in cardiovascular death, 35% reduction in hospitalization for heart failure, and 32% reduction in all-cause mortality—despite only modest A1C reduction of 0.5-0.8%.

SURPASS-2 (n=1,879): This head-to-head trial compared tirzepatide (Mounjaro) against semaglutide (Ozempic) in adults with type 2 diabetes. According to results published in NEJM, Mounjaro achieved A1C reductions of 2.01% (5mg), 2.24% (10mg), and 2.30% (15mg) versus 1.86% with semaglutide 1mg. Weight loss was 7.6 kg, 9.3 kg, and 11.2 kg with tirzepatide doses versus 5.7 kg with semaglutide.

Head-to-Head Limitation: No direct comparator trial exists between Jardiance and Mounjaro. Network meta-analysis suggests Mounjaro is superior for A1C and weight reduction, while Jardiance demonstrates unmatched cardiovascular mortality benefits. The choice depends on individual patient priorities and risk factors.

References

1. Zinman B, et al. Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes – N Engl J Med. 2015;373:2117-28
2. Frías JP, et al. Tirzepatide versus Semaglutide Once Weekly in Patients with Type 2 Diabetes – N Engl J Med. 2021;385:503-515
3. Packer M, et al. Cardiovascular and Renal Outcomes with Empagliflozin in Heart Failure – N Engl J Med. 2020;383:1413-1424
4. Anker SD, et al. Empagliflozin in Heart Failure with a Preserved Ejection Fraction – N Engl J Med. 2021;385:1451-1461
5. FDA Prescribing Information – Jardiance | Mounjaro
6.  American College of Cardiology Clinical Trial Summaries – EMPA-REG OUTCOME | EMPEROR-Reduced