Tag Archives: tirzepatide

Real-World Results of Obesity Pharmacotherapy With Tirzepatide and Semaglutide

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Happy July 4th!

L Gasoyan et al. Obesity 2025; DOI: 10.1002/oby.24331. Open Access! Changes in weight and glycemic control following obesity treatment with semaglutide or tirzepatide by discontinuation status

Methods: This retrospective cohort study used electronic health record data from a large health system in Ohio and Florida to identify adults with overweight or obesity without type 2 diabetes who initiated injectable semaglutide or tirzepatide between 2021 and 2023; 6109 received semaglutide, and 1772 received tirzepatide. Classification as high maintenance doses for semaglutide were 1.7, 2.0, or 2.4 mg and for tirzepatide 10.0, 12.5, or 15.0 mg, and all other dosages classified as low. The study grouped patients who discontinued pharmacotherapy into those who discontinued early (within 3 months of the index date) and late (within 3–12 months)

Key findings:

  • 80.8% had low maintenance dosages
  • Mean (SD) percentage weight reduction at 1 year was 8.7% (9.6%)
  • ~50% discontinued medication within 1 year
  • Patients receiving tirzepatide had more weight loss than those receiving semaglutide (see below). Among patients who did not discontinue obesity pharmacotherapy at year 1, the mean (SD) percentage reduction in weight was 10.9% with semaglutide and 15.3% with tirzepatide
  • In those receiving high dose medication, mean (SD) percentage reduction in weight was 14.7% with semaglutide and 18.0% with tirzepatide
  • Patients who continuing therapy had more weight loss than those who discontinued therapy (see below); Mean (SD) percentage weight reduction at 1 year was 3.6% (8.1%) with early discontinuation, 6.8% (9.1%) with late discontinuation, and 11.9% (9.2%) with non-discontinuation (p < 0.001).

DISCONTINUATION OF THERAPY:

Cumulative incidence of obesity pharmacotherapy discontinuation by index medication. s. Discontinuation of obesity pharmacotherapy was defined as a greater than 90-day gap between exhaustion of previous supply and next dispense or between exhaustion of last supply and end of study follow-up

SEMAGLUTIDE VS TIRZEPATIDE:

RESULTS WITH ONGOING TREATMENT VS TREATMENT DISCONTINUATION:

My take: This study showed higher rates of medication discontinuation in a real world setting compared to prior publications. In addition, the majority were receiving lower doses yet still achieving good results. However, increased discontinuation and lower doses likely explain the discrepancy in weight loss in this cohort which was less than in prior studies. It is important that patients taking these medications receive adequate counseling at the start to improve rates of adherence and long-term outcomes, including mitigation of muscle loss and bone loss.

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Head-to-Head: Tirzepatide Outperforms Semaglutide

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LA Aronne et al. NEJM 2025; DOI: 10.1056/NEJMoa2416394. Tirzepatide as Compared with Semaglutide for the Treatment of Obesity

Methods: In this phase 3b, open-label, controlled “SURMOUNT-5” trial, adult participants (n=751) with obesity but without type 2 diabetes were randomly assigned in a 1:1 ratio to receive the maximum tolerated dose of tirzepatide (10 mg or 15 mg) or the maximum tolerated dose of semaglutide (1.7 mg or 2.4 mg) subcutaneously once weekly for 72 weeks

Key findings:

Discussion Points:

“With both treatments in our trial, as weight reduction increased, greater improvements occurred in cardiometabolic risk factors, including blood pressure, glycemia, and lipid levels, which is consistent with the findings in previous reports.17 The mean differences between tirzepatide and semaglutide in the cardiometabolic risk factors may be clinically relevant considering that reductions in systolic blood pressure of 2 to 5 mm Hg have been shown to reduce the risk of cardiovascular events.”

” As typically observed with incretin-based therapies, gastrointestinal adverse events were predominantly mild to moderate in severity, occurred mostly during dose escalation, and led to treatment discontinuation more often with semaglutide than with tirzepatide.”

My take (borrowed from the authors):  “Treatment with tirzepatide, a dual GIP and GLP-1 receptor agonist, was superior to treatment with semaglutide, a selective GLP-1 receptor agonist, with respect to reduction in body weight and waist circumference.”

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Key Insights on MASLD from Dr. Marialena Mouzaki

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Dr. Marialena Mouzaki recently gave an excellent ground rounds at Children’s Healthcare of Atlanta. My notes below may contain errors in transcription and in omission. Along with my notes, I have included many of her slides (with permission).

Key points:

  • Epidemiology: Metabolic associated steatotic liver disease (MASLD) is very common and increasing in prevalence
  • There is new terminology and new diagnostic thresholds
  • Treatment cornerstone relies on lifestyle changes including diet modifications and exercise. Small weight reductions (10 lbs in adults)/improvement in BMI (z reduction of >0.25) can be beneficial
  • Diet: No specific diet has proven more effective than others (eg. low carb, Mediterranean). Avoiding simple sugars is helpful
  • Exercise: US children do not get enough physical activity (goal 1 hour daily). Exercise has not been studied well for pediatric MASLD but it has been proven to reduce cardiovascular disease and premature death
  • Medications: Medications are not part of routine care for pediatric MASLD in 2025 When they are available, use without lifestyle changes could be detrimental (eg. sarcopenia, worse cardiometabolic profile, nutritional deficiencies)
  • Multiple GLP-1 RA-containing agents appear promising (Semaglutide, tirzepatide, survodutide). Resmetirom is FDA approved for the treatment of MASLD with stage 2-3 fibrosis in adults.
  • Treat comorbidities like diabetes, obstructive sleep apnea (OSA), dyslipidemia and hypertension. Treatment of OSA may help MASLD
  • The leading cause of mortality in adults with MASLD is due to cardiovascular disease

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Tirzepatide: Breakthrough in Obesity and Diabetes Management (SURMOUNT-1 Study at 3 years)

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AM Jastrebofff et al. NEJM 2025; 392: 958-971. Tirzepatide for Obesity Treatment and Diabetes Prevention

Methods: In this phase 3, double-blind, randomized, controlled trial, there were  2539 participants with obesity, of whom 1032 also had prediabetes. They were assigned in a 1:1:1:1 ratio to receive tirzepatide at a once-weekly dose of 5 mg, 10 mg, or 15 mg or placebo.

Key findings:

  • Weight loss: At 176 weeks, the mean percent change in body weight among the participants who received tirzepatide was −12.3% with the 5-mg dose, −18.7% with the 10-mg dose, and −19.7% with the 15-mg dose, as compared with −1.3% among those who received placebo (P<0.001 for all comparisons with placebo).
  • Type 2 Diabetes Reduction: Fewer participants received a diagnosis of type 2 diabetes in the tirzepatide groups than in the placebo group (1.3% vs. 13.3%; hazard ratio, 0.07). After 17 weeks off treatment or placebo, 2.4% of the participants who received tirzepatide and 13.7% of those who received placebo had type 2 diabetes (hazard ratio, 0.12)

My take: This study shows durable effectiveness of tirzepatide over a three year period with no new safety signals.

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Pharmacotherapy for Obesity

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Recently, Dr. Shruthi Arora, an Emory Pediatric Endocrinologist and part of CHOA’s Strong4Life team, provided a terrific review of pediatric obesity pharmacology for our group. 

Here are a few slides from Dr. Arora’s lecture:

General points from this lecture:

  • GLP-1 agents are a huge advance but currently limited by affordability (frequently there is a lack of insurance coverage if there is not T2DM) and availability. In addition, most individuals will regain weight loss when these agents are stopped.
  • GLP-1 agents are not recommended in the following: patients with gastroparesis, and patients with a personal or family history significant for MEN 2 A /MEN 2 B/ Medullary thyroid cancer
  • Long-term data is still needed. These agents have been associated with muscle and bone loss; thus, working to assure a good diet is still very important

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NASPGHAN has a good review/webinar on this topic as well: Pediatric MASLD in the Current Era of Pharmacological and Surgical Obesity Treatment Options. For members, after sign in, you can register and login to this webinar (look under clinical practice tab). This webinar made a lot of useful points (many covered by Dr. Arora too).

  • For GLP-1 agents, due to effects on gastric emptying, they are generally held prior to anesthesia. If they are given weekly, then hold 1 week prior to anesthesia. If it is a daily medication, hold for 1 day prior to anesthesia.
  • Surgery definitely helps improve MASH -though variable responses in patients. SLEEVE gastrectomy is currently the most frequent bariatric surgery
  • There is trouble getting GLP-1 medications. 
  • Limited knowledge regarding long-term effects of cycling of GLP-1 agents.
  • Obesity is a long-term disease –>anticipate long-term treatment

The Wall Street Journal recently published a personal account of using the newer obesity medications. Bradley Olson, 1/12/24: A Weight-Loss Drug Changed My Life. Will It Solve My Problem? (behind a paywall). This article discusses the dramatic improvement experienced by the writer along with his concerns about the cost of the medication and potential for rebound when he can no longer afford it. Two of the figures:

Disclaimer: This blog, gutsandgrowth, assumes no responsibility for any use or operation of any method, product, instruction, concept or idea contained in the material herein or for any injury or damage to persons or property (whether products liability, negligence or otherwise) resulting from such use or operation. These blog posts are for educational purposes only. Specific dosing of medications (along with potential adverse effects) should be confirmed by prescribing physician.  Because of rapid advances in the medical sciences, the gutsandgrowth blog cautions that independent verification should be made of diagnosis and drug dosages. The reader is solely responsible for the conduct of any suggested test or procedure.  This content is not a substitute for medical advice, diagnosis or treatment provided by a qualified healthcare provider. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a condition.

Tirzepatide: Promotes Impressive Weight loss

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Source Study: AM Jastreboff et al NEJM 2022; DOI: 10.1056/NEJMoa2206038. Tirzepatide Once Weekly for the Treatment of Obesity

USA Today (6/6/22): Diabetes drug helps patients lose never-before-seen amounts of weight, study shows

An excerpt:

The drug, called tirzepatide, works on two naturally occurring hormones that help control blood sugar and are involved in sending fullness signals from the gut to the brain...Those taking the highest of three studied doses lost as much as 21% of their body weight – 50-60 pounds in some cases…

Another obesity treatment approved last year called semaglutide, from Novo Nordisk, provides an average of up to about 15% weight loss. Previous generations of diet drugs cut only about 5% of weight and many carried prohibitive side effects…

About 15% of participants who received the active drug dropped out of the 72-week trial, about a third because of gastrointestinal side effects. Twenty-six percent of trial volunteers who received a placebo dropped out.

On May 13, the Food and Drug Administration approved tirzepatide, under the trade name Mounjaro, for the treatment of Type 2 diabetes…The new tirzepatide trial, called SURMOUNT-1, included more than 2,500 volunteers [without diabetes]…Nine out of 10 lost weight, and on the highest dose, 15 mg, they lost an average of 52 pounds each...

It’s too soon to know what price Lilly will set for tirzepatide. Mounjaro, the same drug used to treat diabetes at the same doses, retails for almost $1,000 a month…Semaglutide went on the market last year for weight loss and has been in short supply ever since, Rind said. It costs about $1,600 a month for the 2.4 mg weight loss dose, which is higher than the 1 or 2 mg doses used to treat diabetes. Like other weight loss drugs, semaglutide isn’t covered by many insurance plans. 

My take: This therapy, already approved for Type 2 Diabetes, appears promising for obesity but costly. More time will be needed to understand the safety profile with extended use.

Related blog post: Are We On the Verge of Pharmacologic Management of Obesity (Again)?

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