Feeling tired during the day and wired at night is common for people carrying extra weight. Many Laguna Beach patients say they want to lose weight to feel lighter, sleep better, and get their energy back for the beach trail, morning surf, or simply the school commute. Medical weight loss can help. It combines physician guidance, lab testing, medication when appropriate, and steady coaching to support safe, steady fat loss and healthier routines. As weight comes down and metabolic health improves, most people notice more daytime energy and deeper, more reliable sleep.
Why do weight and sleep affect each other?
Extra body fat can disrupt sleep in several ways. It raises the risk of sleep apnea, a condition where breathing stops and starts during the night. Even mild apnea fragments sleep and leaves people exhausted. Fat tissue also releases inflammatory signals that can make sleep lighter and more restless.
On the other hand, poor sleep makes weight control harder. Short nights drive up hunger hormones, increase cravings for quick carbs, and slow calorie burn the next day. That creates a loop: poor sleep worsens weight, and extra weight worsens sleep. Medical weight loss breaks that loop with targeted care.
How can medical weight loss raise daytime energy?
Energy improves for three practical reasons. First, blood sugar becomes steadier with structured meals, protein-forward plans, and medications that improve insulin response. Steady blood sugar prevents the mid-morning and mid-afternoon crashes that drain focus.
Second, losing even 5 to 10 percent of body weight lowers inflammation and reduces the physical effort of moving through the day. Joints ache less. Climbing the stairs at Gelson’s or walking the kids to Top of the World Elementary takes less out of you.
Third, quality sleep often returns as apnea risk falls. Better sleep means better energy. Patients usually notice a lift in the first 4 to 8 weeks as routines settle and water weight shifts. The bigger stamina gains tend to arrive after the first 10 to 20 pounds.
Can medical weight loss improve sleep quality and snoring?
Yes, and the effect can be meaningful. Weight loss reduces fat around the neck and tongue, which helps keep the airway open at night. Many patients report less snoring by the time they have lost 10 to 15 pounds. For those with diagnosed sleep apnea, weight loss can reduce the number of breathing pauses. Some patients need a CPAP machine for a while, then their sleep study improves and equipment settings can be reduced. A few can discontinue CPAP under physician guidance.
Beyond the airway, structured evening routines support sleep too. Finishing the last meal 3 to 4 hours before bed reduces reflux and nighttime awakenings. Limiting alcohol keeps sleep deeper and more stable. With a plan and support, these small changes are easier to keep.
What does a medical weight loss plan include?
An effective plan starts with a medical visit. That visit covers health history, medication review, vital signs, and lab testing to check thyroid, iron, B12, vitamin D, blood sugar, and cholesterol. Hidden issues, like low iron or an underactive thyroid, can drain energy and stall progress. Treating those issues often gives a quick lift.
Plans typically include a simple nutrition framework with clear targets for protein, fiber, and hydration. Most patients follow a flexible, real-food approach that still fits a date night on Forest Avenue. For some, medications such as GLP-1 receptor agonists help reduce appetite, quiet cravings, and support steady loss. These medicines work best with a basic meal plan and weekly check-ins.
Movement is part of the plan, but it does not have to be extreme. Short, brisk walks on the boardwalk or strength sessions with bands at home are enough at first. The goal is consistency, not punishment. As energy rises, people naturally do more.
What results do Laguna Beach patients usually feel first?
People often notice less bloating and steadier energy in the first two weeks. Cravings fade next. Clothes feel looser by week four. Sleep improvements can show up early if late-night snacking and alcohol cutbacks are part of the plan. Snoring reductions tend to follow visible weight loss.
A common story: a patient drops 12 pounds over six weeks, stops waking at 3 a.m., and stops needing the extra afternoon coffee. They start walking the Montage trail after dinner because they want to, not because they “have to.”
Are weight loss medications safe for sleep and energy?
For the right patient, yes. GLP-1 medications can cause mild nausea in the first weeks, which is manageable with dose steps, hydration, and simple food choices. Most patients rest better as evening snacking ends and reflux settles. Some feel a bit flat in the first week while their appetite resets, then energy rebounds as meals stabilize. These effects are reviewed in follow-ups so the plan can adjust quickly.
Stimulant-based weight pills are generally avoided if sleep is a priority. They can make falling asleep harder. A medical program focuses on tools that support both weight and sleep, not one at the expense of the other.
What lifestyle shifts make the biggest difference locally?
Living in Laguna Beach brings natural advantages. Sunlight in the morning sets the body clock and helps sleep that night. A 10-minute walk at Main Beach or along Heisler Park right after breakfast can lock in that rhythm. Simple local habits work well:
Morning light exposure for 10 minutes and a short walk most days
Four “anchors” for meals: protein, fiber, water, and color on the plate
Cut alcohol to two nights a week or less to reduce sleep disruption
Early dinner on weeknights and kitchen closed by 8 p.m.
Device wind-down 60 minutes before bed and a cool, dark room
These steps support medical weight loss and add up to better energy and sleep without feeling strict.
What if a patient is doing everything right but still feels tired?
There are fixable reasons for stubborn fatigue. Lab results may show low iron, B12, or vitamin D, all common and easy to treat. Thyroid function might be borderline. Sleep apnea may still be present and needs a home sleep test and treatment. Some medications, like certain antidepressants or beta blockers, can affect energy and weight. A medical program looks for these roadblocks, and there is usually a clear next step.
Here is the encouraging part: addressing one hidden issue often lifts energy within days to weeks. Patients appreciate seeing a plan that explains why they felt stuck and how to move forward.
How fast should someone expect to lose weight without harming sleep?
Most adults do well with a pace of about 0.5 to 2 pounds per week. Faster drops can happen at the start due to water shifts, especially if carbs and salt decrease. Sleep problems can flare when people crash diet or push intense evening workouts. A steady plan that protects protein intake, hydration, and a consistent bedtime keeps the body calm and willing to burn fat.
What sets a Laguna Beach medical weight loss program apart for sleep and energy goals?
Local care means local routines. Surf early? The plan accounts for pre-surf fuel and post-surf recovery so morning energy holds. Work in Newport but live in Laguna? The commute is built into the meal timing. Eat out often? Menus at Nick’s, South of Nick’s, and Driftwood Kitchen have go-to choices that fit the plan without feeling deprived.
Follow-up is also key. Brief weekly touchpoints keep progress real and stress low. Patients need flexibility during festival season, school breaks, or travel. The plan bends but does not break.
What signs show the plan is improving energy and sleep?
Track simple markers, not just the scale. Fewer naps. Less afternoon caffeine. Falling asleep within 20 minutes and waking once or not at all. Lower resting heart rate over a few weeks. Fewer headaches. Clearer mornings. These are early wins that often appear before major scale changes.
When should someone consider a formal sleep evaluation?
If a partner notices loud snoring, breathing pauses, or gasping at night, a sleep study is worth it. Morning headaches, dry mouth, or waking unrefreshed despite 7 to 8 hours are also clues. A home sleep test is straightforward, and many patients complete it within a week. Treating apnea accelerates weight loss and restores daytime energy, so it is worth screening early.
What does a first visit at Dolce MD look like?
A typical first visit takes about an hour. It includes a discussion of goals, review of medical history and medications, vitals, and body composition. Labs are ordered the same day. You leave with a simple, written plan and a short list of grocery items and local meal options. If medication is appropriate, the doctor explains how it works, expected benefits, side effects, and costs. Follow-up visits or calls happen weekly at first, then every two to four weeks.
Patients often say the plan feels easier than expected because it fits their real life. That is the goal: fewer decisions, clearer steps, and steady encouragement.
Ready to feel rested and energetic again?
If energy is low or sleep feels broken, medical weight loss can help reset both. You deserve care that fits your life in Laguna Beach and supports real change without extremes. Book a visit with Dolce MD to review your goals, get a clear plan, and start feeling better week by week. Your future self will thank you for taking this step.
In combination with a reduced calorie diet and increased physical activity, semaglutide (as Wegovy) is also indicated in the US for reducing the risk of major adverse cardiovascular events (cardiovascular death, myocardial infarction, or stroke) in adults with established cardiovascular disease and who are either obese or overweight,[15] for reducing excess body weight and maintaining weight reduction long term in obese individuals twelve years of age or older, and for overweight adults with at least one weight-related comorbid condition.[15][34][35] After stopping semaglutide, individuals on average regain about two-thirds (67%) of the weight they lost during treatment within the following year.[36][37]
In October 2025, the US FDA further expanded the indication for semaglutide (as Rybelsus) to reduce the risk of major adverse cardiovascular events (cardiovascular death, non-fatal myocardial infarction, or non-fatal stroke) in adults with type2 diabetes who are at high risk for these events.[14][38]
In the EU, semaglutide is indicated for the treatment of adults with insufficiently controlled type2 diabetes as an adjunct to diet and exercise as monotherapy when metformin is considered inappropriate due to intolerance or contraindications,[16][17] in addition to other medicinal products for the treatment of diabetes.[16][17]
In the EU, semaglutide (as Wegovy) is further indicated as an adjunct to a reduced-calorie diet and increased physical activity for weight management, including weight loss and weight maintenance, in adults with obesity (initial BMI ≥ 30 kg/m2) or who are overweight (initial BMI ≥ 27 kg/m2) and have at least one weight-related comorbidity such as dysglycemia (pre-diabetes or type2 diabetes), hypertension, dyslipidemia, or cardiovascular disease.[18] It is also indicated as an adjunct to a reduced-calorie diet and increased physical activity for weight management in adolescents (aged twelve years of aged and older) with obesity and body weight above 60 kg (130 lb).[18]
GLP-1 regulates digestion and blood sugar. The small intestine releases GLP-1 when food is eaten. It reduces hunger, signals fullness, stimulates insulin, and inhibits glucagon, maintaining glucose levels.
Semaglutide is a glucagon-like peptide-1 receptor agonist.[13][14][15] The drug decreases blood sugar levels. The decrease is theorized to be caused by the mimicking of glucagon-like peptide-1 (GLP-1), an incretin.[45] It also appears to enhance growth of pancreatic beta cells, which are responsible for insulin production and release.[27][46] Additionally, it inhibits the production of glucagon, the hormone that increases glycogenolysis (release of stored carbohydrate from the liver) and gluconeogenesis (synthesis of new glucose). It reduces food intake by lowering appetite and slowing down digestion in the stomach,[26] helping reduce body weight.[47][48]
Schematic representation of the structures of semaglutide and liraglutide, compared to GLP-1
Semaglutide is chemically similar to human GLP-1.[49] The first six amino acids of GLP-1 are missing.[49] Substitutions are made at GLP positions 8 and 34 (semaglutide positions 2 and 28), where alanine and lysine are replaced by 2-aminoisobutyric acid and arginine, respectively.[49] The substitution of the alanine prevents chemical breakdown by dipeptidyl peptidase-4.[50] The lysine at GLP position 26 (semaglutide position 20) has a long chain attached, ending with a chain of 18 carbon atoms and a carboxyl group.[50] This increases the drug's binding to blood protein (albumin), which enables longer presence in the blood circulation.[50]
Semaglutide's half-life in the blood is about seven days (165–184 hours).[27][51]
In the 1970s, Jens Juul Holst and Joel Habener began research on the GLP-1 hormone, initially in relation to duodenal ulcer disease.[52] They were examining hormones secreted during eating, and testing them on pig pancreases, leading to the discovery of GLP-1's significant potency in 1988. Their work, which later contributed significantly to diabetes and obesity treatments, earned them and Daniel J. Drucker the 2021 Warren Alpert Foundation Prize.[52]
Research continued, and in 1993, Michael Nauck managed to infuse GLP-1 into people with type2 diabetes, stimulating insulin while inhibiting glucagon and bringing blood glucose to normal levels. However, treating diabetes with GLP-1 hormones resulted in significant side effects, leading researchers financed by Novo Nordisk to start looking to develop a suitable compound for therapeutic use.[52] In 1998, a team of researchers at Novo Nordisk led by Lotte Bjerre Knudsen developed liraglutide, a glucagon-like peptide-1 receptor agonist that could be used to treat diabetes.[53] This was followed by the development of semaglutide by a team of researchers at Novo Nordisk, including Jesper Lau, Thomas Kruse, and Paw Bloch.[54][55][56]
In June 2008, a phase II clinical trial began studying semaglutide, a once-weekly diabetes therapy as a longer-acting alternative to liraglutide.[57][58] It was given the brand name Ozempic. Clinical trials started in January 2016 and ended in May 2017.[23][59]
The US Food and Drug Administration (FDA) approved semaglutide based on evidence from seven clinical trials of 4087 participants with type2 diabetes.[42] The trials were conducted at 536 sites in 33 countries, including Canada, Mexico, Russia, Ukraine, Turkey, India, South Africa, Japan, Hong Kong, multiple European countries, Argentina, and the United States.[42] In two of these trials (NCT02054897[60] and NCT02305381[61]), participants were randomly assigned to receive either semaglutide or placebo injection weekly.[42] Neither the participant nor the health care provider knew which treatment was being given until after the trials were completed.[42] Treatment was given for 30 weeks.[42] In the other five trials (NCT01930188,[62] NCT01885208,[63] NCT02128932,[64] NCT02207374,[65] and NCT02254291[66]), participants were randomly assigned to receive either semaglutide or another anti-diabetic medication, and the participant and provider knew which medication was being given in four trials.[42] Treatment was given for 30 weeks or 56 weeks.[42] In each trial, HbA1c was measured from the start of the trial to the end of the trial and compared between the semaglutide group and the other groups.[42]
The FDA also considered data from one separate trial (NCT01720446[67]) of 3297 participants with type2 diabetes who were at high risk for cardiovascular events.[42] This trial was conducted in 20 countries: multiple European countries, Russia, Turkey, Brazil, Israel, Malaysia, Mexico, Thailand, Taiwan, Canada, and the United States.[42] The participants were randomly assigned to receive semaglutide or placebo.[42] Neither the participant nor the health care provider knew which treatment was being given.[42] Treatment was given for 104 weeks (2 years), and the occurrence of cardiovascular events, including heart attacks, strokes, and hospitalization due to unstable angina (near heart attack) were recorded and compared in the two groups of participants.[42]
In March 2021, in a phase III randomized, double-blind trial, 1,961 adults with a body mass index of 30 or greater were assigned in a 2:1 ratio to a treatment with once-weekly subcutaneous semaglutide or placebo, plus lifestyle intervention. The trials occurred at 129 sites in 16 countries in Asia, Europe, North America, and South America. The mean percentage change in body weight at week 68 was −14.9% in the semaglutide group vs −2.4% with placebo, for an estimated treatment difference of −12.4 percentage points (95% CI, −13.4 to −11.5).[68][69][70][71]
A 2022 review of anti-obesity treatments found that semaglutide as well as tirzepatide (which has an overlapping mechanism of action) were more promising than previous anti-obesity drugs, although less effective than bariatric surgery.[72]
In March 2024, the US Food and Drug Administration expanded the indication for semaglutide (brand name Wegovy) to reduce the risk of cardiovascular death, heart attack, and stroke in adults with cardiovascular disease and who are either obese or overweight.[35] The efficacy and safety of semaglutide for this indication were studied in a multi-national, multi-center, placebo-controlled double-blind trial that randomly assigned over 17,600 participants to receive either semaglutide (Wegovy) or placebo.[35] Participants in both groups also received standard-of-care medical treatment (e.g., management of blood pressure and cholesterol) and healthy lifestyle counseling (including diet and physical activity).[35] Semaglutide (Wegovy) significantly reduced the risk of major adverse cardiovascular events (cardiovascular death, heart attack, and stroke), which occurred in 6.5% of participants who received semaglutide (Wegovy) compared to 8% of participants who received placebo.[35]
In December 2016, a new drug application was filed with the US Food and Drug Administration (FDA), and in October 2017, a FDA advisory committee approved it unanimously.[73] In December 2017, the injectable version with the brand name Ozempic was approved in the US for use by people with diabetes,[30][74] and, in January 2018, in Canada.[75] In February 2018, authorization was granted in the European Union,[16][76] in March 2018 in Japan,[77] and in August 2019 in Australia.[1][3]
A version of semaglutide to treat diabetes that can be taken orally (Rybelsus) was approved for medical use in the US in September 2019,[78][79] and in the European Union in April 2020.[17] In January 2023, the US FDA prescription label for Rybelsus was updated to reflect that it can be used as a first-line treatment for adults with type2 diabetes.[80]
In June 2021, a higher-dose version for injectable use, sold under the brand name Wegovy, was approved by the FDA as an anti-obesity medication for long-term weight management in adults.[15] In January 2022, Wegovy was approved for medical use in the European Union.[18][21]
Due to high costs, some health plans in the US do not cover weight-loss drugs like semaglutide and tirzepatide.[81][82][83] In the United States, as of 2024, about half of private employer-sponsored plans cover these drugs,[84] Federal Medicare Part D does not cover weight-loss drugs, and only a few federally-funded, state-administered Medicaid plans do so.[85]
Semaglutide is expected to become patent-free in the United States no earlier than December 2031,[86] and in Europe and Japan in that same year.[87] The Chinese patent was scheduled to expire in 2026, but a court ruled in 2022 that all patents on semaglutide were invalid. Novo Nordisk appealed the ruling.[88] In Brazil, the Supreme Court refused to extend semaglutide's patent protection, which expires in 2026.[89] In Canada, Novo Nordisk failed to pay a required patent maintenance fee and the semaglutide patent will expire in January 2026.[87] Four companies, including Apotex, Sandoz, and Hims & Hers Health are expected to release generic versions of semaglutide in Canada.[90][91][92]
Semaglutide had the highest earnings from sales of medications in the US in 2023, with expenditures of US$38.6 billion.[93]
In the US, Wegovy has a list price of $1,349.02 per month as of 2022, suggesting that because of the high costs many people "who could most benefit from weight loss may be unable to afford such expensive drugs".[94] High costs of Ozempic prompted some insurance companies to investigate and refuse to cover individuals with what the companies considered was insufficient evidence to support a diabetes diagnosis, alleging off-label prescribing for weight loss.[95] In 2023, Ozempic, the semaglutide injection used for type 2 diabetes treatment, had list price of one-month supply of $936 in the US, $169 in Japan, $147 in Canada, $144 in Switzerland, $103 in Germany and the Netherlands, $96 in Sweden, $93 in the UK, and $87 in Australia; France had the lowest price at $83.[96][97]
In the UK, semaglutide is available on NHS prescription for diabetes at nominal or no cost to the individual.[98] It is also available for obesity, limited to treatment for two years.[99] In Finland, semaglutide is included in the national price regulation scheme and is available by prescription; however, for people with type 2 diabetes and a BMI over 27, part of the cost is covered by Kela, the Finnish Social Insurance Institution.[100] In Australia, semaglutide is available on the Pharmaceutical Benefits Scheme prescription for diabetes at the regular co-payment rates of $31.60, or $7.70 for concession card holders.[101]
High demand caused worldwide supply shortages of semaglutide in 2023;[95] new UK prescriptions were not issued during the shortage. Novo Nordisk revealed in April 2024, that to meet the enormous demand for semaglutide, it was running its production facilities 24/7; it had budgeted $6 billion in 2024 to expand its crowded and congested facilities; and it had hired over 10,000 new employees in 2023 alone.[102]
By 2023, Novo Nordisk had become the most valuable corporation in the European Union, worth more than US$500 billion, and accounted for almost all recent economic growth in Denmark.[103] The large amounts of foreign currency earned by Novo Nordisk from Wegovy and Ozempic sales, when converted to Danish krone, have generally exerted substantial upward pressure on the value of the krone, making it necessary for Danmarks Nationalbank to maintain lower interest rates than the European Central Bank.[104][105] Poor clinical trial results published by Novo Nordisk in December 2024 contributed to a drop in the krone's value.[106]
Profits from Novo Nordisk generate returns for the Novo Nordisk Foundation, which holds the controlling stake in Novo Nordisk. The profits results in increased Danish tax revenues and employment. Novo Nordisk added 3,500 jobs in Denmark in 2022, bringing the total in the country to 21,000 employees, out of 59,000 worldwide.[107]
In October 2023, there were reports of counterfeit Ozempic pens being sold in Europe.[108] The pens possibly contained insulin, and led to several people being hospitalised with hypoglycemia and seizures.[109][110][111] In December 2023, the FDA issued a warning about counterfeit Ozempic in the US.[112]
In the US, compounding pharmacies may prepare compounded versions of a drug on the Food and Drug Administration's (FDA) drug shortages list if the compounded drug meets certain conditions detailed in federal law.[113][114][115] The FDA declared a shortage for Ozempic and Wegovy (but not Rybelsus) starting in August 2022.[116][117]
The US National Association of Boards of Pharmacy claims that there are tens of thousands of online pharmacies operating out of compliance with state and federal regulations or the association's recommendations.[118] Novo Nordisk has taken action against several compounding pharmacies producing bad versions of the drug, with impurities, the wrong amount of active ingredient, or even no active ingredient.[118] Some compounded versions have been found to contain salts of semaglutide, including the sodium and the acetate in an attempt to avoid the patent of the base semaglutide product.[119] These are not evaluated for safety and effectiveness by the FDA and thus are considered not shown to be safe or effective.[120]
A 2014 meta-analysis found that semaglutide may be effective in lowering liver enzymes (transaminitis) and improving certain radiologically observed features of metabolic dysfunction–associated steatotic liver disease.[121] The French national health care insurance system database had previously suggested that one to three years of use of glucagon-like peptide-1 receptor agonists like exenatide, liraglutide, and dulaglutide may be linked with increased occurrence of thyroid cancer. Semaglutide belongs to the same family of medicine. A meta-analysis involving data from 37 randomized controlled trials and 19 real-world studies (46,719 individuals) showed that semaglutide use over 18 months was not associated with increased risk of any cancer, supported by high-quality evidence.[122]
In March 2023, a Novo Nordisk official said, based on a randomized, double-blind study (NCT03548935[123]) funded by the company, that people using semaglutide to lose weight regained two-thirds of their original weight loss one year (52 weeks) after discontinuing use of the drug. After two years (120 weeks), the patients retained roughly one-third of their original weight loss (5.6% of the original 17.3% loss).[124][125]
In June 2025, the European Medicines Agency recommended that the product information for semaglutide medicines be updated to include non-arteritic anterior ischemic optic neuropathy as a side effect with a frequency of 'very rare',[130] while the World Health Organization concluded that the Risk Management Plan for semaglutide should be revised to include non-arteritic anterior ischemic optic neuropathy as a potential risk.[131]
A 2025 observational study reported a modest increased risk of a serious eye condition in people with diabetes taking glucagon-like peptide-1 (GLP-1) receptor agonists.[132] The analysis found that individuals using the medications had a slightly higher incidence of neovascular age-related macular degeneration compared to similar individuals not on the medications.[133] After one year, 0.2% of users of GLP-1 medications developed neovascular age-related macular degeneration versus 0.1% among non-users. The study, which analyzed health data from nearly 140,000 individuals in Canada, controlled for socioeconomic and health-related factors. The average participant age was 66. Since the risk factors for neovascular age-related macular degeneration overlap with those of people prescribed GLP-1 medications, such as diabetes and related conditions, researchers investigated this potential link following reports of other eye-related side effects in people on GLP-1 therapies.
In the STEP-HFpEF trial including people with obesity and heart failure with preserved ejection fraction, weight loss was associated with improvements in heart failure symptoms and functional capacity.[134] An observational study on people with obesity and type 2diabetes and heart failure with preserved ejection fraction, semaglutide had about a 42% lower risk of hospitalization for heart failure and all-cause death combined compared with sitagliptin.[135]
A 2024 systematic review of six studies found that "although reductions in body weight and fat mass were evident, changes in lean mass were minor".[136]
^World Health Organization (2025). The selection and use of essential medicines, 2025: WHO Model List of Essential Medicines, 24th list. Geneva: World Health Organization. doi:10.2471/B09474. hdl:10665/382243. License: CC BY-NC-SA 3.0 IGO.
^Claxton G, Rae M, Damico A, Winger A, Wager E (November 2024). "Health Benefits In 2024: Higher Premiums Persist, Employer Strategies For GLP-1 Coverage And Family-Building Benefits". Health Affairs. 43 (11): 1491–1501. doi:10.1377/hlthaff.2024.01006. PMID39381848.
^Tichy EM, Hoffman JM, Tadrous M, Rim MH, Cuellar S, Clark JS, et al. (July 2024). "National trends in prescription drug expenditures and projections for 2024". American Journal of Health-System Pharmacy. 81 (14): 583–598. doi:10.1093/ajhp/zxae105. PMID38656319.
^Dutta D, Kumar M, Shivaprasad KS, Kumar A, Sharma M (June 2022). "Impact of semaglutide on biochemical and radiologic measures of metabolic-dysfunction associated fatty liver disease across the spectrum of glycaemia: A meta-analysis". Diabetes & Metabolic Syndrome. 16 (6) 102539. doi:10.1016/j.dsx.2022.102539. PMID35709586. S2CID249584781.
^Krüger N, Schneeweiss S, Fuse K, Matseyko S, Sreedhara SK, Hahn G, et al. (31 August 2025). "Semaglutide and Tirzepatide in Patients With Heart Failure With Preserved Ejection Fraction". JAMA. 334 (14): 1255–1266. doi:10.1001/jama.2025.14092. PMID40886075.
^Bikou A, Dermiki-Gkana F, Penteris M, Constantinides TK, Kontogiorgis C (April 2024). "A systematic review of the effect of semaglutide on lean mass: insights from clinical trials". Expert Opinion on Pharmacotherapy. 25 (5): 611–619. doi:10.1080/14656566.2024.2343092. PMID38629387.
^Daniel S, Waggett S, Lyles E, Sagut P, Shamaei Zadeh P, Marcelletti A, et al. (April 2025). "A Retrospective Comparative Analysis of Cutaneous Adverse Reactions in GLP-1 Agonist Therapies". Journal of Drugs in Dermatology. 24 (4): 413–415. doi:10.36849/JDD.8605. PMID40196945.
Clinical trial number NCT03574597 for "Semaglutide Effects on Heart Disease and Stroke in Patients With Overweight or Obesity (SELECT)" at ClinicalTrials.gov
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From Pubchem
Developed by Eli Lilly and Company, tirzepatide was approved for treatment of diabetes in the U.S. in May 2022,[9][13] in the European Union in September 2022,[11] in Canada in November 2022,[19] and in Australia in December 2022.[2] The U.S. Food and Drug Administration (FDA) considers it a first-in-class medication.[20][21] The FDA approved it for weight loss in November 2023.[16][22] Also in November 2023, the U.K. Medicines and Healthcare products Regulatory Agency revised the indication for tirzepatide (as Mounjaro) to include the treatment for weight management and weight loss.[8][23] In December 2024, the FDA revised the indication for tirzepatide (as Zepbound) to include the treatment of moderate to severe obstructive sleep apnea.[10][17] In 2023, tirzepatide was the 110th-most commonly prescribed medication in the U.S., with more than six million prescriptions.[24][25]
Tirzepatide (as Mounjaro) is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes.[9][13]
Tirzepatide (as Zepbound) is indicated, alongside a reduced-calorie diet and increased physical activity, for long-term weight reduction in adults with obesity or overweight with at least one weight-related comorbidity.[10][16] Zepbound is also approved for the treatment of moderate-to-severe obstructive sleep apnea in adults with obesity.[10]
Preclinical, phase I, and phase II clinical trials indicated that tirzepatide exhibits adverse effects similar to those of other established GLP-1 receptor agonists, such as dulaglutide (sold as Trulicity) and semaglutide (sold as Wegovy, Ozempic, and Rybelsus). These effects occur largely in the gastrointestinal tract.[26] The most frequently observed are nausea, diarrhea, and vomiting, which increased in incidence with the dosage amount (that is, the higher the dose, the higher the likelihood of side effects). The number of patients who discontinued taking tirzepatide also increased as the dosage increased, with patients taking 15 mg having a 25% discontinuation rate vs 5.1% for 5 mg patients and 11.1% for dulaglutide.[27][clarification needed] To a slightly lesser extent, patients also reported reduced appetite.[26] Other side effects reported were dyspepsia, constipation, abdominal pain, dizziness, and hypoglycemia.[28][29]
A systematic review published in 2024 found that tirzepatide is well tolerated and not associated with pancreatitis.[30]
Tirzepatide has a greater affinity to GIP receptors than to GLP-1 receptors, and this dual agonist behavior has been shown to produce greater reductions of hyperglycemia compared to a selective GLP-1 receptor agonist.[14]Signaling studies reported that tirzepatide mimics the actions of natural GIP at the GIP receptor.[34] At the GLP-1 receptor, though, tirzepatide shows bias toward cAMP (a messenger associated with regulation of glycogen, sugar, and lipid metabolism) generation rather than β-arrestin recruitment. This combination of preference toward GIP receptor and distinct signaling properties at GLP-1 suggest this biased agonism increases insulin secretion.[34] Tirzepatide has been reported to increase levels of adiponectin, an adipokine involved in the regulation of both glucose and lipid metabolism, with a maximum increase of 26% from baseline after 26 weeks, at the 10 mg dosage.[14]
Tirzepatide is an analog of the human GIP hormone with a C20fatty diacid portion attached, used to optimise the uptake and metabolism of the compound.[31] The fatty-diacid section (eicosanedioic acid) is linked via a glutamic acid and two (2-(2-aminoethoxy)ethoxy)acetic acid units to the side chain of the lysine residue. This arrangement allows for a much longer half-life, extending the time between doses, because of its high affinity to albumin.[35]
The synthesis of tirzepatide was first disclosed in patents filed by Eli Lilly and Company in 2016.[36] This uses standard solid phase peptide synthesis, with an allyloxycarbonylprotecting group on the lysine at position 20 of the linear chain of amino acids, allowing a final set of chemical transformations in which the sidechain amine of that lysine is derivatized with the lipid-containing fragment.
Large-scale manufacturing processes have been reported for this compound.[37]
After completing the SURPASS-2 trial (NCT03987919), the company announced in April 2022 that tirzepatide had successfully met its clinical endpoints in obese and overweight participants without diabetes.[39]
In industry-funded preliminary trials, tirzepatide showed minor improvement of reductions (2.01%–2.30% depending on dosage) in glycated hemoglobin tests relative to the injected GLP-1 analog semaglutide (1.86%).[40] A 10 mg dose has also been shown to be effective in reducing insulin resistance, with a reduction of around 8% from baseline, measured using HOMA2-IR (computed with fasting insulin).[14] Fasting levels of insulin-like growth factor (IGF) binding proteins such as IGFBP1 and IGFBP2 increased after tirzepatide treatment, increasing insulin sensitivity.[14]
The FDA approved tirzepatide based on evidence from nine clinical trials of 7,769 participants with type 2 diabetes, of whom 5,415 received tirzepatide.[41] The trials were conducted at 673 sites in 24 countries, including Argentina, Australia, Brazil, Canada, India, Israel, Japan, Mexico, Russian Federation, South Korea, Taiwan, European Union, and the United States (including Puerto Rico).[41] All nine trials were used to assess its safety, and five were used to evaluate its efficacy.[41] The five used in efficacy evaluation included 6,263 adult participants with type 2 diabetes.[41] Four additional trials (NCT03131687, NCT03311724, NCT03861052, and NCT03861039) were included in the safety evaluation, for a total of 7,769 adult participants with type 2 diabetes; therefore, the number of participants representing efficacy findings may differ from the number representing safety findings due to different pools of study participants analyzed for efficacy and safety.[41] Tirzepatide's benefits for the treatment of adult participants with type 2 diabetes were primarily evaluated in five clinical trials.[41] In two of these (NCT03954834 and NCT04039503), participants were randomly assigned to receive either tirzepatide or placebo injection weekly.[41] Neither the patient nor the healthcare provider knew which treatment was being given until after the trials were completed.[41] Treatment was given for 40 weeks.[41] In the other three trials (NCT3987919, NCT03882970, and NCT03730662), participants were randomly assigned to receive either tirzepatide or another antidiabetic medication, and the patient and provider knew which medication was being given.[41] Treatment was given for 40 weeks to 104 weeks.[41] In each trial, HbA1c was measured from the start to the end of the trial and compared between the tirzepatide group and the other groups.[41]
Tirzepatide's efficacy for chronic weight management (weight reduction and maintenance) in combination with a reduced-calorie diet and increased physical activity was established in two randomized, double-blind, placebo-controlled trials of adults with obesity or overweight with at least one weight-related condition.[16] These studies measured weight reduction after 72 weeks in 2,519 participants who received either 5 mg, 10 mg, or 15 mg of tirzepatide once weekly and 958 participants who received weekly placebo injections.[16] In both trials, after 72 weeks of treatment, participants who received tirzepatide at all three dose levels experienced a statistically significant reduction in body weight compared to those who received placebo, and greater proportions of participants who received tirzepatide achieved at least 5% weight reduction compared to placebo.[16]
In August 2024, the SURMOUNT-1 three-year study (176-week treatment period) found that tirzepatide reduced the risk of developing type 2 diabetes by 94% in adults with pre-diabetes and obesity or overweight.[42]
A 2021 meta-analysis found that over one year of clinical use, tirzepatide was superior to dulaglutide, semaglutide, insulin degludec, and insulin glargine in improving blood sugar and obesity.[43]
In a phase III double-blind, randomized, controlled trial supported by Eli Lilly, nondiabetic adults with a body mass index of 30 or more, or 27 or more and at least one weight-related complication, excluding diabetes, were randomized to receive once-weekly, subcutaneous tirzepatide (5 mg, 10 mg, or 15 mg) or placebo. The mean percentage change in weight at week 72 was −15.0% (95% confidence interval [CI], −15.9 to −14.2) with 5-mg weekly doses of tirzepatide, −19.5% (95% CI, −20.4 to −18.5) with 10-mg doses, and −20.9% (95% CI, −21.8 to −19.9) with 15-mg doses. Weight change in the placebo group was −3.1% (95% CI, −4.3 to −1.9).[44][45][46]
In July 2022, the Committee for Medicinal Products for Human Use of the European Medicines Agency adopted a positive opinion, recommending granting a marketing authorization for the medicinal product Mounjaro, intended for the treatment of type2 diabetes.[47] Tirzepatide was approved for medical use in the European Union in September 2022.[11][48]
In December 2024, the FDA approved tirzepatide (Zepbound) as the first medication to be used in the treatment of moderate to severe obstructive sleep apnea.[17][49][50] The FDA granted the application for tirzepatide (Zepbound) fast track, priority review, and breakthrough therapy designations for the treatment of moderate to severe obstructive sleep apnea.[17] The FDA granted the approval of Zepbound to Eli Lilly.[17]
In the U.S., some compounding pharmacies prepare compounded versions of a drug on the FDA's drug shortages list if the compounded drug meets certain conditions detailed in federal law.[51][52][53] The FDA declared a shortage of tirzepatide in December 2022.[54] It declared the shortage over in October 2024, but enforcement was delayed until the end of 2024, after a lawsuit by compounding pharmacies challenged the declaration.[55][56]
The U.S. National Association of Boards of Pharmacy says there are tens of thousands of online pharmacies operating out of compliance with state and federal regulations or the association's recommendations.[57] The FDA has not evaluated these for safety and effectiveness and they are thus considered not to have been shown to be safe or effective.[58]
In a phase III trial, tirzepatide demonstrated clinically significant benefits among participants with obesity and heart failure with preserved ejection fraction.[59][60] Over two years of follow-up, tirzepatide decreased participants' risk of major cardiovascular (CV) complications—a combined endpoint including urgent heart failure visits, hospitalizations, more frequent diuretic treatment, and CV mortality—by 38% compared to a placebo.[61] An observational study on patients with obesity and type 2 diabetes and heart failure with preserved ejection fraction reported that tirzepatide had a lower risk of hospitalization for heart failure and all-cause death combined than sitagliptin.[62][63] In a 72-week, phase IIIb open-label head-to-head trial of adults with obesity without diabetes, tirzepatide at the maximum tolerated dose produced greater mean weight loss than semaglutide and larger reductions in waist circumference, while gastrointestinal adverse events were the most common with both drugs.[64]
After stopping treatment with tirzepatide for obesity, people on average regain more than half (53%) of the weight they lost during treatment within a year.[65][66]
^ abc"Mounjaro EPAR". European Medicines Agency (EMA). 18 July 2022. Archived from the original on 12 December 2022. Retrieved 2 January 2023. Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
^World Health Organization (2019). "International nonproprietary names for pharmaceutical substances (INN): recommended INN: list 81". WHO Drug Information. 33 (1). hdl:10665/330896.
^ abUS patent 9474780, Bokvist BK, Coskun T, Cummins RC, Alsina-Fernandez J, "GIP and GLP-1 co-agonist compounds", issued 25 October 2016, assigned to Eli Lilly and Co
^"Mounjaro: Pending EC decision". European Medicines Agency. 22 July 2022. Archived from the original on 28 July 2022. Retrieved 30 July 2022. Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
^Aronne LJ, Horn DB, le Roux CW, Ho W, Falcon BL, Gomez Valderas E, et al. (July 2025). "Tirzepatide as Compared with Semaglutide for the Treatment of Obesity". The New England Journal of Medicine. 393 (1): 26–36. doi:10.1056/NEJMoa2416394. PMID40353578.
