What Is Tirzepatide Good For?

FDA-Approved Indications

Tirzepatide has two primary FDA-approved uses, each representing a significant advance over existing treatments. The approval was based on clinical trials involving over 15,000 participants that demonstrated superior efficacy compared to both placebo and active comparators including semaglutide.

Type 2 Diabetes Management

Tirzepatide received FDA approval for type 2 diabetes in May 2022, based on the SURPASS clinical trial program. This program enrolled over 10,000 participants across 8 major trials and demonstrated that tirzepatide produces some of the largest glucose reductions ever achieved with a single medication.

Exceptional Glycemic Control

The primary benefit of tirzepatide in diabetes is its exceptional glucose-lowering effect. Across the SURPASS trials, tirzepatide consistently reduced HbA1c by 1.9-2.5% from baseline, with many participants achieving HbA1c levels below 7% (the general target) and even below 5.7% (normal range). In SURPASS-1, which compared tirzepatide to placebo, 87-92% of participants on tirzepatide achieved HbA1c below 7%, compared to 20% on placebo. These results exceed those of most other diabetes medications.

What makes these results even more impressive is that they were achieved across diverse populations including people with newly diagnosed diabetes, those with long-standing disease, those on no background therapy, and those on multiple medications. The glucose-lowering effect appears within the first few weeks of treatment and reaches maximum effect by 20-24 weeks. Importantly, the effect is glucose-dependent—tirzepatide stimulates insulin secretion only when blood glucose is elevated, substantially reducing hypoglycemia risk.

Superior to Existing Treatments

Multiple SURPASS trials directly compared tirzepatide to other diabetes medications. SURPASS-2 compared tirzepatide to semaglutide 1 mg weekly (at that time the most effective GLP-1 agonist), showing superior glucose lowering with tirzepatide (2.0-2.5% vs 1.9% HbA1c reduction). SURPASS-3 compared tirzepatide to insulin degludec (a long-acting basal insulin), showing superior glucose control with tirzepatide despite insulin being titrated to target. SURPASS-4 compared tirzepatide to insulin glargine in people with high cardiovascular risk, again showing superiority.

These head-to-head comparisons establish tirzepatide as one of the most effective glucose-lowering agents available. The only interventions that produce comparable glucose reductions are intensive insulin regimens (multiple daily injections with careful titration), but these carry high hypoglycemia risk and cause weight gain, whereas tirzepatide has low hypoglycemia risk and produces substantial weight loss.

Dramatic Weight Loss in Diabetes

Unlike most diabetes medications that cause weight gain (insulin, sulfonylureas, thiazolidinediones) or modest weight loss (metformin, SGLT2 inhibitors), tirzepatide produces dramatic weight loss. In the SURPASS trials conducted at diabetes doses, participants lost an average of 7-12 kg depending on dose, with the highest dose (15 mg) producing 12.4 kg weight loss over 40 weeks. This weight loss is clinically transformative because excess weight is a major driver of insulin resistance and diabetes progression.

The weight loss with tirzepatide in diabetes populations is substantially greater than with other diabetes medications. In SURPASS-2, tirzepatide 15 mg produced 12.4 kg weight loss compared to 6.2 kg with semaglutide 1 mg—double the weight loss. This superior weight loss likely contributes to tirzepatide's superior glucose lowering, as weight loss improves insulin sensitivity and reduces the burden on pancreatic beta cells.

Cardiovascular Risk Factor Improvements

Beyond glucose and weight, tirzepatide improves multiple cardiovascular risk factors. Across the SURPASS trials, tirzepatide reduced systolic blood pressure by 5-10 mmHg, reduced triglycerides by 20-30%, increased HDL cholesterol by 5-10%, and reduced inflammatory markers including C-reactive protein by 30-40%. These improvements suggest potential cardiovascular benefits, though dedicated cardiovascular outcomes trials are needed to confirm this (SURPASS-CVOT is ongoing with results expected in 2024-2025).

Potential for Diabetes Remission

Perhaps most exciting, tirzepatide may enable diabetes remission in some people. In SURPASS-1, 42-52% of participants achieved HbA1c below 5.7% (the threshold for normal glucose metabolism) without diabetes medications. While this doesn't necessarily represent true remission (glucose may rise again if tirzepatide is stopped), it demonstrates that tirzepatide can restore near-normal glucose metabolism in many people with type 2 diabetes. This raises the possibility that early intervention with tirzepatide might prevent or reverse diabetes progression.

Chronic Weight Management

In November 2023, tirzepatide received FDA approval for chronic weight management at doses up to 15 mg weekly (marketed as Zepbound). This approval was based on the SURMOUNT clinical trial program, which demonstrated weight loss exceeding that of any other obesity medication and approaching results typically seen with bariatric surgery.

Unprecedented Weight Loss

The SURMOUNT-1 trial enrolled 2,539 adults with obesity (BMI ≥30) or overweight (BMI ≥27) with at least one weight-related comorbidity, but without diabetes. Participants received tirzepatide (5 mg, 10 mg, or 15 mg weekly) or placebo, both combined with lifestyle intervention. After 72 weeks, the results were remarkable: average weight loss of 15.0% with 5 mg, 19.5% with 10 mg, and 20.9% with 15 mg, compared to 3.1% with placebo.

Even more impressive, 89% of participants on 15 mg lost at least 5% of body weight (vs 35% placebo), 83% lost at least 10% (vs 9% placebo), 71% lost at least 15% (vs 3% placebo), and 50% lost at least 20% (vs 1% placebo). Nearly one-third (30%) lost 25% or more of their body weight. These results approach or match those typically seen with bariatric surgery, which has long been considered the gold standard for substantial, sustained weight loss.

Superior to Semaglutide

While no head-to-head trial has directly compared tirzepatide 15 mg to semaglutide 2.4 mg for weight management, indirect comparisons using similar trial designs and populations suggest tirzepatide produces approximately 4-6 percentage points greater weight loss. Tirzepatide 15 mg produces ~21% weight loss compared to semaglutide 2.4 mg's ~15-17% weight loss. This difference is clinically meaningful—it represents the difference between good and exceptional outcomes for many patients.

Body Composition Changes

DEXA scan analyses from SURMOUNT trials show that approximately 70-75% of weight lost with tirzepatide is fat mass, with 25-30% being lean mass. This ratio is similar to semaglutide and actually favorable compared to weight loss through caloric restriction alone. Importantly, visceral adipose tissue (the metabolically harmful fat surrounding internal organs) appears to be preferentially reduced, with MRI studies showing 35-45% reductions in visceral fat—greater than the reduction in subcutaneous fat.

This preferential loss of visceral fat is particularly beneficial because visceral fat is strongly associated with insulin resistance, inflammation, cardiovascular disease, and metabolic dysfunction. The reduction in visceral fat likely contributes substantially to the metabolic improvements seen with tirzepatide, including improvements in insulin sensitivity, lipid profiles, and inflammatory markers.

Cardiometabolic Benefits

The weight loss achieved with tirzepatide translates into improvements across multiple cardiometabolic risk factors. In SURMOUNT-1, tirzepatide reduced waist circumference by 12-15 cm, systolic blood pressure by 7-10 mmHg, triglycerides by 25-30%, and inflammatory markers by 35-45%. For participants with prediabetes at baseline, tirzepatide reduced progression to type 2 diabetes by 94% over 72 weeks—nearly complete prevention. Among those with prediabetes, 96% reverted to normoglycemia with tirzepatide 15 mg compared to 62% with placebo.

Quality of Life Improvements

Beyond objective health measures, tirzepatide significantly improves quality of life. Participants reported improvements in physical functioning (ability to perform daily activities, exercise tolerance), reductions in bodily pain, improvements in general health perceptions, and improvements in mental health measures. These quality of life improvements appear to result from both the physical effects of weight loss (reduced joint pain, improved mobility, better sleep, increased energy) and psychological effects (improved body image, increased self-efficacy, reduced depression and anxiety).

Weight Loss Maintenance

The SURMOUNT-4 trial specifically examined weight loss maintenance. Participants first received open-label tirzepatide for 36 weeks, losing an average of 20.9% of body weight. They were then randomized to continue tirzepatide or switch to placebo for an additional 52 weeks. Those continuing tirzepatide maintained their weight loss and lost an additional 5.5% (total 25.3% from baseline), while those switched to placebo regained 14.0% (net loss of only 9.9% from baseline).

These results demonstrate that tirzepatide's weight loss benefits are maintained with continued treatment but largely disappear when treatment is stopped. This has led to discussions about whether obesity should be viewed as a chronic disease requiring long-term pharmacotherapy, similar to hypertension or diabetes. The alternative view is that tirzepatide should be used as a tool to achieve weight loss, after which intensive lifestyle modification can maintain the loss, though the SURMOUNT-4 results suggest this is challenging for most people.

Investigational and Off-Label Uses

Beyond its approved indications, tirzepatide is being investigated for several other conditions where its metabolic effects may provide benefit.

Non-Alcoholic Fatty Liver Disease (NAFLD/NASH)

Non-alcoholic fatty liver disease affects approximately 25% of adults globally and can progress to non-alcoholic steatohepatitis (NASH), cirrhosis, and liver failure. Weight loss is the primary treatment, making tirzepatide's dramatic weight loss effects particularly relevant. Early studies show that tirzepatide significantly reduces liver fat content, with MRI studies demonstrating 50-60% reductions in hepatic fat. Markers of liver inflammation and injury (ALT, AST) improve substantially.

Phase 2 trials examining tirzepatide specifically for NASH are ongoing. If successful, tirzepatide could become an important treatment for NASH, a condition for which no FDA-approved pharmacotherapies currently exist. The mechanism likely involves both direct effects of weight loss on liver metabolism and potential direct effects of GIP and GLP-1 receptor activation on hepatic function.

Obstructive Sleep Apnea

Obesity is the primary risk factor for obstructive sleep apnea (OSA), and weight loss is an effective treatment. The SURMOUNT trials included assessments of sleep apnea symptoms and found that tirzepatide significantly improved sleep quality and reduced daytime sleepiness. A dedicated trial (SURMOUNT-OSA) is examining whether tirzepatide can reduce the apnea-hypopnea index (the primary measure of OSA severity) and potentially allow some patients to discontinue CPAP therapy.

Preliminary results suggest tirzepatide reduces the apnea-hypopnea index by approximately 50-60% in patients with moderate to severe OSA, with many participants achieving resolution of OSA (AHI <5 events per hour). These improvements correlate with weight loss and reductions in neck circumference. If confirmed in larger trials, tirzepatide could become an important treatment option for OSA, potentially reducing the need for CPAP therapy in some patients.

Heart Failure with Preserved Ejection Fraction (HFpEF)

Heart failure with preserved ejection fraction is strongly associated with obesity and metabolic dysfunction, and few effective treatments exist. The dramatic weight loss and metabolic improvements with tirzepatide suggest potential benefits for HFpEF. Trials are examining whether tirzepatide improves symptoms, functional capacity, and quality of life in patients with HFpEF and obesity.

The mechanism may involve reductions in cardiac workload due to weight loss, improvements in myocardial metabolism, reductions in inflammation and fibrosis, and favorable effects on neurohormonal activation. If successful, tirzepatide could fill an important therapeutic gap for HFpEF, a condition that affects millions and for which treatment options are limited.

Polycystic Ovary Syndrome (PCOS)

Polycystic ovary syndrome affects 5-10% of women of reproductive age and is characterized by irregular menstrual cycles, hyperandrogenism, and often insulin resistance and obesity. Weight loss improves both metabolic and reproductive outcomes in PCOS. Small pilot studies suggest tirzepatide may be beneficial, with weight loss leading to restoration of regular menstrual cycles, improvements in androgen levels, and enhanced fertility.

However, tirzepatide is contraindicated during pregnancy due to potential teratogenic effects observed in animal studies. Women of reproductive age using tirzepatide for PCOS must use effective contraception. Additionally, because tirzepatide can restore ovulation in women with PCOS, there is a risk of unintended pregnancy if contraception is not used consistently. Larger randomized trials are needed to confirm tirzepatide's efficacy for PCOS and establish optimal treatment protocols.

Chronic Kidney Disease

Obesity and diabetes are major risk factors for chronic kidney disease, and weight loss and glucose control can slow kidney disease progression. Trials are examining whether tirzepatide can slow progression of chronic kidney disease in patients with type 2 diabetes and kidney disease. The mechanism may involve improved glycemic control, blood pressure reduction, weight loss, and direct anti-inflammatory and anti-fibrotic effects on the kidney.

If successful, tirzepatide could join SGLT2 inhibitors and ACE inhibitors/ARBs as cornerstone therapies for diabetic kidney disease. Whether tirzepatide provides kidney protection in people without diabetes remains to be determined, though the mechanisms suggest it might.

Who Benefits Most from Tirzepatide?

While tirzepatide is effective across diverse populations, certain groups appear to derive particular benefit:

People with Type 2 Diabetes and Obesity

Individuals with both diabetes and obesity represent an ideal population for tirzepatide, as it addresses both conditions with exceptional efficacy. The combination of superior glucose lowering and dramatic weight loss makes tirzepatide particularly valuable for this group. Many patients can achieve both glycemic targets and transformative weight loss, potentially allowing reduction or discontinuation of other diabetes medications.

People Who Have Failed Other Weight Loss Interventions

Many people with obesity have made repeated attempts at weight loss through diet, exercise, and even other medications but have been unable to achieve or maintain meaningful weight loss. For these individuals, tirzepatide's superior efficacy (20-25% weight loss at the highest dose) may provide the additional support needed to achieve their goals. The medication doesn't replace lifestyle modification but rather facilitates adherence to reduced-calorie diets by suppressing appetite and enhancing satiety.

People Considering Bariatric Surgery

For people considering bariatric surgery, tirzepatide offers a non-surgical alternative that produces comparable weight loss for many patients. While surgery remains more effective for the most severe obesity and may be preferred by some patients, tirzepatide provides an option for those who prefer to avoid surgery, have contraindications to surgery, or want to try medical management first. Some patients may use tirzepatide as a bridge to surgery, achieving weight loss that reduces surgical risk.

People with Obesity and Multiple Comorbidities

Individuals with obesity and multiple weight-related comorbidities (hypertension, dyslipidemia, sleep apnea, NAFLD, osteoarthritis, prediabetes) often see improvements across multiple conditions with tirzepatide-induced weight loss. This can lead to reduced medication burden, improved quality of life, and potentially reduced healthcare costs. The challenge is ensuring these individuals have access to tirzepatide given its high cost.

Limitations and Considerations

While tirzepatide is highly effective, it's important to understand its limitations:

Not Effective for Everyone

Approximately 10-15% of people do not achieve meaningful weight loss (defined as ≥5% of body weight) with tirzepatide, even at the maximum dose. The reasons for non-response are not fully understood but may include genetic factors affecting GIP and GLP-1 receptor function, differences in gut microbiome composition, or behavioral factors. There are currently no reliable predictors of who will respond well to tirzepatide.

Weight Regain After Discontinuation

Most people regain substantial weight when tirzepatide is discontinued. The SURMOUNT-4 trial showed that participants regained about two-thirds of lost weight within one year of stopping tirzepatide. This raises questions about treatment duration—should tirzepatide be viewed as a long-term therapy for obesity, similar to how we treat hypertension or diabetes? Or should it be used as a tool to achieve weight loss, after which intensive lifestyle modification maintains the loss?

Cost and Access

The high cost of tirzepatide (over $1,000 per month in the United States) limits access for many people who could benefit. Insurance coverage varies widely, with many plans covering Mounjaro for diabetes but not Zepbound for weight management. This has led to widespread off-label prescribing of Mounjaro for weight loss. Addressing cost and access barriers will be crucial for realizing tirzepatide's public health potential.

Long-Term Safety Unknown

While tirzepatide has been studied for up to 2-3 years in clinical trials, longer-term safety data are limited. Questions remain about potential risks with decades of use, particularly regarding thyroid cancer (a theoretical concern based on animal studies), pancreatitis, gallbladder disease, and effects on bone health and muscle mass. Post-marketing surveillance will be important for detecting rare adverse events that may not have been apparent in clinical trials.

Cardiovascular Outcomes Data Pending

Unlike semaglutide, which has demonstrated cardiovascular benefits in dedicated outcomes trials, tirzepatide's cardiovascular effects remain to be definitively established. The SURPASS-CVOT trial is ongoing, with results expected in 2024-2025. Until these results are available, semaglutide has an advantage for patients prioritizing proven cardiovascular protection, particularly those with established cardiovascular disease.