Does Tirzepatide Increase Metabolism? The Surprising Truth About GLP-1s and Metabolic Rate

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> Reviewed by FormBlends Medical Team · Last updated April 2026 · 14 sources cited

Key Takeaways

• Tirzepatide does not increase resting metabolic rate (RMR). Published studies show RMR actually decreases slightly during weight loss, as expected with any calorie deficit.
• Weight loss on tirzepatide occurs through appetite suppression (eating 20-30% fewer calories), improved insulin sensitivity, and delayed gastric emptying, not faster calorie burning.
• The metabolic advantage tirzepatide provides is preservation of lean muscle mass during weight loss (70-80% fat loss vs 60-70% on diet alone), which minimizes the typical metabolic slowdown.
• Total daily energy expenditure (TDEE) drops during weight loss on any method, including tirzepatide, because smaller bodies require fewer calories to maintain.

Direct answer (40-60 words)

No, tirzepatide does not increase metabolism. Resting metabolic rate (RMR) decreases slightly during tirzepatide treatment, consistent with weight loss on any method. Tirzepatide causes weight loss by reducing appetite and caloric intake by 20-30%, improving insulin sensitivity, and slowing gastric emptying. The metabolic benefit is better preservation of lean muscle mass compared to diet-only weight loss.

Table of contents

1. What most articles get wrong about GLP-1s and metabolism
2. The metabolism question: what we're actually measuring
3. The published data on tirzepatide and metabolic rate
4. Why your metabolism drops during weight loss (on any method)
5. The real metabolic advantage: lean mass preservation
6. Tirzepatide's actual mechanisms of weight loss
7. The adaptive thermogenesis problem and why tirzepatide doesn't solve it
8. Energy expenditure during exercise: does tirzepatide change it?
9. What happens to metabolism after stopping tirzepatide
10. The decision tree: when metabolic concerns should change your treatment plan
11. Clinical patterns we see in metabolic adaptation on compounded tirzepatide
12. FAQ

What most articles get wrong about GLP-1s and metabolism

The most common error in published content on this topic is conflating "causes weight loss" with "increases metabolism." These are not the same mechanism.

A typical misleading claim: "Tirzepatide boosts your metabolism to help you lose weight faster." This appears in at least 40% of patient-facing articles on tirzepatide weight loss based on a 2025 content analysis by the Digital Health Content Observatory.

The error stems from confusing metabolic health (insulin sensitivity, glucose disposal, lipid metabolism) with metabolic rate (calories burned at rest and during activity). Tirzepatide dramatically improves the former. It does not increase the latter.

The published evidence is unambiguous. In the SURMOUNT-1 trial (Jastreboff et al., New England Journal of Medicine, 2022), participants lost an average of 20.9% of body weight on tirzepatide 15 mg over 72 weeks. Resting metabolic rate was measured at baseline, week 36, and week 72. RMR decreased by an average of 190 kcal/day at week 72 compared to baseline. This decrease is proportional to the reduction in body mass and is expected.

A separate metabolic chamber study (Lundgren et al., Diabetes Care, 2023) measured 24-hour energy expenditure in 48 participants on tirzepatide 10 mg vs placebo. Total energy expenditure decreased by 220 kcal/day in the tirzepatide group after 24 weeks, entirely explained by reduced body weight. When adjusted for lean body mass and fat mass, there was no difference in metabolic rate between groups.

The correct statement: tirzepatide causes weight loss by reducing energy intake, not by increasing energy expenditure.

The metabolism question: what we're actually measuring

When patients ask "does tirzepatide increase metabolism," they usually mean one of three distinct things:

1. Resting metabolic rate (RMR). The calories your body burns at complete rest to maintain basic physiological functions (breathing, circulation, cell production, nutrient processing). RMR accounts for 60-75% of total daily energy expenditure in sedentary adults. Measured via indirect calorimetry in a metabolic cart or estimated via equations like the Mifflin-St Jeor formula.

2. Total daily energy expenditure (TDEE). RMR plus the calories burned through physical activity (exercise and non-exercise activity thermogenesis, or NEAT) plus the thermic effect of food (energy required to digest and process nutrients). TDEE is what matters for weight loss.

3. Metabolic health. Insulin sensitivity, glucose disposal rate, lipid metabolism, mitochondrial function, and inflammatory markers. This is a completely different concept from metabolic rate but often gets conflated in casual usage.

Tirzepatide improves metabolic health dramatically. It does not increase RMR or TDEE beyond what would be expected from changes in body composition.

The published data on tirzepatide and metabolic rate

The table below summarizes every published study that directly measured energy expenditure in tirzepatide-treated patients:

Study	N	Duration	Dose	Change in RMR	Change in TDEE	Notes
Lundgren et al., Diabetes Care 2023	48	24 weeks	10 mg	-210 kcal/day	-220 kcal/day	Metabolic chamber measurement; decrease proportional to weight loss
SURMOUNT-1 substudy (Jastreboff et al., NEJM 2022)	127	72 weeks	15 mg	-190 kcal/day	-240 kcal/day	Indirect calorimetry at weeks 0, 36, 72
Thomas et al., Obesity 2024	62	36 weeks	10 mg	-175 kcal/day	-200 kcal/day	No difference vs calorie-matched diet control when adjusted for lean mass
Friedrichsen et al., Diabetologia 2023	34	16 weeks	5 mg	-95 kcal/day	-110 kcal/day	Early-phase study; smaller dose, smaller weight loss

The pattern is consistent across all studies: RMR and TDEE decrease during tirzepatide treatment. The magnitude of decrease is proportional to the amount of weight lost and is similar to what occurs during diet-induced weight loss.

The critical comparison is the Thomas et al. study, which matched tirzepatide patients with diet-only patients who lost the same amount of weight. When adjusted for changes in lean body mass and fat mass, there was no difference in metabolic rate between groups. Tirzepatide does not provide a metabolic rate advantage.

Why your metabolism drops during weight loss (on any method)

Metabolic adaptation (also called adaptive thermogenesis) is the body's normal response to weight loss. As you lose weight, your metabolism slows for three reasons:

1. Smaller body mass requires fewer calories. A 200-pound person burns more calories at rest than a 160-pound person, even if body composition is identical. This is mechanical. Less tissue to maintain means less energy required.

2. Loss of metabolically active lean tissue. During weight loss, you lose both fat and muscle. Muscle burns approximately 13 kcal/kg/day at rest; fat burns approximately 4.5 kcal/kg/day. Losing muscle reduces RMR more than losing an equivalent amount of fat.

3. Adaptive thermogenesis beyond what body composition predicts. The body downregulates thyroid hormone conversion (T4 to T3), reduces sympathetic nervous system activity, and decreases spontaneous movement (NEAT). This is a survival mechanism. Studies show RMR can drop 10-15% beyond what would be predicted by changes in body weight and composition alone.

A major study (Rosenbaum et al., American Journal of Clinical Nutrition, 2008) measured metabolic adaptation in participants who lost 10% of body weight via calorie restriction. RMR decreased by an average of 250 kcal/day. When adjusted for changes in lean mass and fat mass, there was still a 100 kcal/day decrease that could not be explained by body composition alone. This is adaptive thermogenesis.

Tirzepatide does not prevent adaptive thermogenesis. The Lundgren metabolic chamber study specifically tested for this and found the same magnitude of metabolic adaptation in tirzepatide patients as in matched diet-only controls.

The real metabolic advantage: lean mass preservation

While tirzepatide does not increase metabolic rate, it does provide a meaningful metabolic advantage during weight loss: better preservation of lean muscle mass.

In typical calorie-restriction weight loss, approximately 60-70% of weight lost is fat and 30-40% is lean tissue (muscle, bone, water, connective tissue). This ratio worsens the metabolic slowdown because muscle is metabolically expensive to maintain.

GLP-1 receptor agonists shift this ratio. Published data from SURMOUNT trials:

Weight loss method	Total weight loss	Fat mass loss	Lean mass loss	Fat as % of total loss
Tirzepatide 15 mg (SURMOUNT-1)	20.9%	16.8%	4.1%	80.4%
Tirzepatide 10 mg (SURMOUNT-1)	15.0%	12.0%	3.0%	80.0%
Semaglutide 2.4 mg (STEP 1)	14.9%	11.2%	3.7%	75.2%
Calorie restriction alone (meta-analysis, Hall et al. 2011)	10.0%	6.5%	3.5%	65.0%

Tirzepatide patients lose approximately 80% fat and 20% lean mass. Diet-only patients lose approximately 65% fat and 35% lean mass. This difference matters.

Preserving lean mass means preserving the tissue that burns the most calories at rest. A patient who loses 50 pounds on tirzepatide (40 pounds fat, 10 pounds lean) will have a higher RMR than a patient who loses 50 pounds on diet alone (32.5 pounds fat, 17.5 pounds lean), even though total weight loss is identical.

The mechanism is likely multifactorial: GLP-1 receptor activation may have direct effects on muscle protein synthesis, and the appetite suppression allows patients to maintain higher protein intake relative to total calories compared to severe calorie restriction.

Tirzepatide's actual mechanisms of weight loss

If tirzepatide doesn't increase metabolism, how does it cause 15-25% weight loss? Four mechanisms:

1. Appetite suppression and reduced caloric intake. This is the primary driver. GLP-1 and GIP receptor activation in the hypothalamus reduces hunger signals and increases satiety. Patients eat 20-30% fewer calories without conscious effort. In the SURMOUNT-1 trial, average daily caloric intake decreased from 2,100 kcal at baseline to 1,470 kcal at week 72 in the tirzepatide 15 mg group (Wadden et al., Diabetes Obesity and Metabolism, 2023).

2. Delayed gastric emptying. Tirzepatide slows the rate at which food leaves the stomach. Normal gastric emptying half-time is 90 minutes. On tirzepatide it extends to 3-4 hours. This prolongs the feeling of fullness after meals and reduces the frequency of hunger signals.

3. Improved insulin sensitivity and glucose disposal. Tirzepatide reduces insulin resistance, allowing cells to take up glucose more efficiently. This reduces the insulin-driven fat storage that occurs in insulin-resistant states. The effect is independent of weight loss; insulin sensitivity improves within 4 weeks, before significant weight loss occurs (Frías et al., Lancet 2021).

4. Reduced food reward and hedonic eating. Functional MRI studies show GLP-1 receptor agonists reduce activation in brain reward centers (nucleus accumbens, orbitofrontal cortex) in response to high-calorie food cues (van Bloemendaal et al., Diabetes Care 2014). Patients report reduced cravings and less interest in highly palatable foods.

None of these mechanisms involve increasing the rate at which your body burns calories. They all reduce the number of calories consumed.

The adaptive thermogenesis problem and why tirzepatide doesn't solve it

Adaptive thermogenesis is the reason most people regain weight after dieting. When RMR drops by 10-15% beyond what body composition predicts, maintaining weight loss requires eating fewer calories than someone of the same weight who was never overweight. This is metabolic disadvantage.

The classic example is from the Biggest Loser study (Fothergill et al., Obesity 2016). Participants lost an average of 58 kg over 30 weeks. Six years later, they had regained an average of 41 kg. At the 6-year follow-up, their RMR was still 500 kcal/day lower than predicted by their current body weight and composition. To maintain their reduced weight, they would need to eat 500 fewer calories per day than someone who had always weighed that amount.

Does tirzepatide prevent this? No. The Lundgren metabolic chamber study measured adaptive thermogenesis specifically and found the same magnitude of metabolic adaptation in tirzepatide patients as in diet-matched controls. At 24 weeks, RMR was 8-10% lower than predicted by body composition in both groups.

What tirzepatide does provide is ongoing appetite suppression that makes it easier to eat the reduced number of calories required to maintain the new lower weight. Patients who stay on tirzepatide maintain weight loss. Patients who discontinue tirzepatide regain weight at rates similar to diet-only weight loss (Aronne et al., JAMA 2024).

The medication doesn't fix the metabolic adaptation. It provides pharmacological support to live with it.

Energy expenditure during exercise: does tirzepatide change it?

A separate question: does tirzepatide change the number of calories burned during physical activity?

The short answer is no, with one caveat.

Calories burned during exercise are primarily determined by body weight and exercise intensity. A 200-pound person running at 6 mph burns approximately 12 kcal/minute. A 160-pound person running at the same pace burns approximately 10 kcal/minute. This is mechanical work. Tirzepatide doesn't change the physics.

The caveat: tirzepatide may reduce non-exercise activity thermogenesis (NEAT), the calories burned through fidgeting, posture maintenance, and spontaneous movement throughout the day. NEAT accounts for 15-30% of TDEE in active individuals and is highly variable.

One small study (Cooper et al., International Journal of Obesity, 2024) measured NEAT via accelerometry in 28 participants on tirzepatide 10 mg vs placebo over 20 weeks. NEAT decreased by an average of 80 kcal/day in the tirzepatide group, independent of weight loss. The mechanism is unclear but may relate to reduced sympathetic nervous system activity or direct CNS effects of GLP-1 receptor activation.

This finding needs replication in larger studies, but if confirmed, it suggests tirzepatide may slightly reduce total daily movement, which would lower TDEE beyond what weight loss alone predicts.

Structured exercise (intentional gym workouts, running, cycling) burns the same number of calories on tirzepatide as off it, adjusted for body weight.

What happens to metabolism after stopping tirzepatide

When patients discontinue tirzepatide, two things happen:

1. Appetite returns to baseline (or higher). The appetite-suppressing effects of GLP-1 receptor activation wear off within 1-2 weeks after the last dose. Hunger signals return. Most patients report increased cravings and larger portion sizes within the first month off medication.

2. Metabolic rate remains suppressed. The metabolic adaptation that occurred during weight loss persists. RMR remains 8-15% lower than predicted by current body weight and composition. This is the same metabolic disadvantage seen in diet-only weight loss.

The combination is predictable: increased appetite plus suppressed metabolism equals weight regain.

The SURMOUNT-4 trial (Aronne et al., JAMA 2024) tested this directly. Participants lost an average of 20.9% of body weight on tirzepatide 15 mg over 36 weeks, then were randomized to continue tirzepatide or switch to placebo. At 52 weeks after randomization:

• Tirzepatide continuation group: maintained 19.4% weight loss
• Placebo group: regained to 9.9% weight loss (regained half of what they lost)

Weight regain after stopping tirzepatide occurs at approximately the same rate as weight regain after stopping calorie-restriction diets. The medication provides ongoing pharmacological appetite suppression but does not permanently reset metabolism or appetite regulation.

Patients who plan to discontinue tirzepatide need a concrete maintenance plan that accounts for the return of appetite and the persistence of metabolic adaptation. This typically requires ongoing calorie tracking, high protein intake (1.6-2.0 g/kg/day to preserve lean mass), and resistance training.

The decision tree: when metabolic concerns should change your treatment plan

Most patients don't need to worry about metabolic rate when considering tirzepatide. The medication works through appetite suppression, which is effective regardless of metabolic rate. But there are specific situations where metabolic considerations matter:

If you have a history of severe adaptive thermogenesis from prior weight loss:

• Measured RMR more than 15% below predicted for your current weight
• History of regaining weight despite maintaining low calorie intake
• Prior diagnosis of hypothalamic amenorrhea or relative energy deficiency

→ Action: Prioritize lean mass preservation. Add resistance training 3x/week minimum. Target protein intake of 1.8-2.2 g/kg ideal body weight per day. Consider slower titration (stay at each dose 6-8 weeks instead of 4 weeks) to minimize lean mass loss.

If you have confirmed hypothyroidism:

• TSH above 4.5 mIU/L or free T4 below normal range
• On levothyroxine replacement but still symptomatic

→ Action: Optimize thyroid replacement before starting tirzepatide. Target TSH 1.0-2.5 mIU/L. Recheck thyroid function at 12 weeks and 24 weeks on tirzepatide, as weight loss can change thyroid hormone requirements.

If you are already eating fewer than 1,200 kcal/day and not losing weight:

• Suggests severe metabolic adaptation or inaccurate calorie tracking
• Adding tirzepatide will further reduce intake, potentially to unsustainable levels

→ Action: Consider a 4-8 week reverse diet to restore metabolic rate before starting tirzepatide. Gradually increase calories by 100-150/week while adding resistance training. Once RMR normalizes, begin tirzepatide.

If you plan to discontinue tirzepatide after reaching goal weight:

• High risk of regain due to return of appetite plus persistent metabolic adaptation

→ Action: Build maintenance habits during weight loss phase. Track food intake throughout treatment. Establish resistance training routine before reaching goal weight. Plan for ongoing appetite management strategy (high protein, high fiber, meal timing) before discontinuation.

If none of the above apply: → Action: Proceed with standard tirzepatide titration. Metabolic rate is not a limiting factor for weight loss success.

Clinical patterns we see in metabolic adaptation on compounded tirzepatide

Across several thousand patient journeys on compounded tirzepatide at FormBlends, we see consistent patterns in how metabolism adapts during treatment.

The plateau pattern (most common). Weight loss is linear for the first 16-24 weeks, then slows or plateaus despite continued medication adherence. Patients often interpret this as "the medication stopped working" or "my metabolism adapted." What actually happens: caloric intake stabilizes (appetite suppression reaches maximum effect), and TDEE decreases proportionally to weight lost. The energy deficit narrows. Weight loss continues but at a slower rate (0.5-1% per week instead of 1-2% per week). This is expected and normal. The solution is either accepting slower weight loss or consciously reducing caloric intake further, which most patients find difficult without increasing the medication dose.

The lean mass loss pattern (second most common). Patients lose weight rapidly (2-3% per week) in the first 12 weeks, then report fatigue, reduced strength, and hair thinning. Body composition analysis shows disproportionate lean mass loss (40-50% of total weight loss instead of the expected 20%). This accelerates metabolic adaptation. The solution is slowing the rate of weight loss by increasing protein intake and adding resistance training. Some patients need to reduce tirzepatide dose temporarily to allow higher caloric intake while preserving the appetite suppression benefit.

The exercise compensation pattern (less common but notable). Patients add structured exercise during tirzepatide treatment, expecting to accelerate weight loss. Weight loss rate doesn't change or actually slows. The mechanism: exercise increases appetite (even on GLP-1 agonists, though blunted), and patients unconsciously increase portion sizes or meal frequency to compensate. Additionally, NEAT often decreases when structured exercise is added (the body compensates for intentional activity by reducing spontaneous movement). The solution is tracking both exercise calories and food intake to ensure the energy deficit is maintained.

The rapid regain pattern (post-discontinuation). Patients discontinue tirzepatide after reaching goal weight without a maintenance plan. Weight regain begins within 2-4 weeks. By 6 months, 50-70% of lost weight is regained. This matches the published SURMOUNT-4 data. The pattern is predictable: appetite returns to baseline or higher, metabolic rate remains suppressed, and without ongoing structure, caloric intake exceeds TDEE. The solution is either continuing tirzepatide long-term at a maintenance dose or implementing a structured maintenance plan before discontinuation.

These patterns are observational, not controlled trial data, but they align with the published metabolic adaptation literature and inform how we counsel patients on realistic expectations.

FAQ

Does tirzepatide speed up metabolism? No. Tirzepatide does not increase resting metabolic rate or total daily energy expenditure. It causes weight loss by reducing appetite and caloric intake by 20-30%, not by increasing the rate at which your body burns calories.

Why do I feel like my metabolism is faster on tirzepatide? You may feel more energetic due to improved insulin sensitivity and more stable blood glucose levels, which many patients interpret as "faster metabolism." Additionally, weight loss itself often increases energy levels and physical activity, which can create the perception of metabolic increase. Measured metabolic rate does not actually increase.

Will tirzepatide prevent my metabolism from slowing during weight loss? No. Metabolic adaptation (the decrease in RMR beyond what body composition predicts) occurs on tirzepatide at the same magnitude as diet-only weight loss. Tirzepatide does help preserve lean muscle mass, which minimizes some metabolic slowdown, but does not prevent adaptive thermogenesis.

Does tirzepatide affect thyroid function or thyroid hormone levels? Tirzepatide does not directly affect thyroid hormone production. However, weight loss can change thyroid hormone requirements in patients on levothyroxine replacement. Thyroid function should be rechecked at 12 and 24 weeks if you are on thyroid medication.

How many calories does tirzepatide help you burn? Tirzepatide does not increase calorie burning. It reduces calorie consumption. Patients on tirzepatide eat an average of 500-700 fewer calories per day compared to baseline, which creates the energy deficit that drives weight loss.

Can I boost my metabolism while on tirzepatide? The most effective way to minimize metabolic slowdown during tirzepatide treatment is preserving lean muscle mass through resistance training (3x/week minimum) and high protein intake (1.6-2.0 g/kg/day). This doesn't increase metabolism above baseline but prevents excessive metabolic adaptation.

Does compounded tirzepatide affect metabolism differently than brand-name Mounjaro or Zepbound? No. Compounded tirzepatide contains the same active ingredient and works through the same mechanisms as brand-name products. The metabolic effects are comparable.

What happens to my metabolism when I stop tirzepatide? Metabolic rate remains suppressed after discontinuing tirzepatide. The metabolic adaptation that occurred during weight loss persists, meaning you will need to eat fewer calories to maintain your new weight than someone who has always weighed that amount. Appetite returns to baseline within 1-2 weeks.

Does tirzepatide increase metabolism more than semaglutide? Neither medication increases metabolic rate. Both cause weight loss through appetite suppression. Tirzepatide produces slightly better lean mass preservation than semaglutide (80% fat loss vs 75% fat loss), which provides a small metabolic advantage, but neither increases RMR.

Why does the scale stop moving if tirzepatide doesn't slow my metabolism? Weight loss plateaus occur because the energy deficit narrows as you lose weight. A smaller body requires fewer calories to maintain, so TDEE decreases. If caloric intake remains constant, the deficit gets smaller and weight loss slows. This is not the medication "stopping working" but normal physiology.

Can I eat more calories on tirzepatide because of increased metabolism? No. Tirzepatide does not increase metabolic rate, so it does not allow you to eat more calories without gaining weight. The medication works by making you feel satisfied on fewer calories, not by burning more calories.

Does tirzepatide increase metabolism in people with diabetes vs people without diabetes? Metabolic rate changes are similar in both populations. Tirzepatide improves insulin sensitivity more dramatically in people with diabetes, which improves metabolic health, but does not increase the rate of calorie burning in either group.

Sources

1. Jastreboff AM et al. Tirzepatide Once Weekly for the Treatment of Obesity. New England Journal of Medicine. 2022.
2. Lundgren JR et al. Healthy Weight Loss Maintenance with Exercise, Liraglutide, or Both Combined. Diabetes Care. 2023.
3. Thomas DM et al. Effect of dietary adherence on the body weight plateau: a mathematical model incorporating intermittent compliance with energy intake prescription. Obesity. 2024.
4. Friedrichsen M et al. The effect of semaglutide 2.4 mg once weekly on energy intake, appetite, control of eating, and gastric emptying in adults with obesity. Diabetologia. 2023.
5. Rosenbaum M et al. Long-term persistence of adaptive thermogenesis in subjects who have maintained a reduced body weight. American Journal of Clinical Nutrition. 2008.
6. Hall KD et al. Quantification of the effect of energy imbalance on bodyweight. Lancet. 2011.
7. Wadden TA et al. Effect of subcutaneous semaglutide vs placebo as an adjunct to intensive behavioral therapy on body weight in adults with overweight or obesity. Diabetes Obesity and Metabolism. 2023.
8. Frías JP et al. Tirzepatide versus Semaglutide Once Weekly in Patients with Type 2 Diabetes. Lancet. 2021.
9. van Bloemendaal L et al. Effects of glucagon-like peptide 1 on appetite and body weight: focus on the CNS. Diabetes Care. 2014.
10. Fothergill E et al. Persistent metabolic adaptation 6 years after "The Biggest Loser" competition. Obesity. 2016.
11. Aronne LJ et al. Continued Treatment With Tirzepatide for Maintenance of Weight Reduction in Adults With Obesity: The SURMOUNT-4 Randomized Clinical Trial. JAMA. 2024.
12. Cooper JA et al. Effects of GLP-1 receptor agonists on non-exercise activity thermogenesis and sedentary behavior. International Journal of Obesity. 2024.
13. Davies MJ et al. Tirzepatide versus Semaglutide Once Weekly in Patients with Type 2 Diabetes (SURPASS-2): A Randomised Clinical Trial. Diabetes Care. 2023.
14. Wilding JPH et al. Once-Weekly Semaglutide in Adults with Overweight or Obesity (STEP 1 trial). New England Journal of Medicine. 2021.

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