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  • Writer's pictureDr. Ndidi Ufondu, DPM

New Drug Retatrutide Offers Hope for Managing Diabetes, Obesity and Related Foot Pain



As podiatrists, we frequently see firsthand the damage obesity and diabetes can inflict on foot health. Carrying excess weight and having chronically high blood sugar levels puts immense stress on the feet, leading to issues like chronic pain, loss of sensation, ulcers, infections, and even amputation in severe cases.


That’s why we’re excited by an investigational new medication called retatrutide. Early phase 2 and 3 clinical trial results show retatrutide may offer unparalleled weight loss and blood sugar improvement. This suggests the drug could provide tangible benefits for foot pain, neuropathy, and other complications in people living with obesity or diabetes.


How Does Retatrutide Work?


Retatrutide is an injectable drug that activates receptors for three appetite-regulating hormones: glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP), and glucagon. It essentially tricks the body into feeling more satiated and full while also improving glucose metabolism.


In phase 2 clinical trials conducted by drugmaker Eli Lilly, retatrutide has been shown to deliver:

  • Up to 24% weight loss (nearly 60 lbs) in patients with obesity after 48 weeks

  • Up to 17% weight loss in patients with both obesity and type 2 diabetes after 36 weeks

  • Reductions in HbA1c up to 2% in patients with type 2 diabetes


These results exceed those seen for other medications like semaglutide (Ozempic, Wegovy) and tirzepatide (Mounjaro). Experts believe retatrutide’s unique triple-hormone mechanism explains its increased efficacy for weight loss and glycemic control compared to drugs targeting only GLP-1 or GLP-1/GIP.


Phase 3 trials assessing retatrutide's long-term efficacy and safety are currently underway, with results expected in late 2025.


Link Between Obesity, Diabetes and Foot Pain


The potential foot pain relief benefits of retatrutide become clearer when you understand how excess weight and uncontrolled blood sugar impact the feet:


  • Obesity – Carrying extra pounds puts abnormally high mechanical stress on the foot structures, leading to issues like:

    1. Plantar fasciitis - inflammation of the tissue supporting the arch

    2. Joint pain and arthritis in the ankles, knees, and feet

    3. Increased risk of injuries, sprains, and fractures


  • Diabetes – Chronically elevated blood glucose damages nerves and blood vessels. This makes the feet much more prone to:

    1. Peripheral neuropathy - nerve damage causing numbness or burning pain

    2. Impaired circulation, increasing risk of non-healing ulcers

    3. Loss of protective sensation, leading to unchecked ulcers


By promoting weight loss and improving blood sugar control, medications like retatrutide may significantly reduce patients’ risk of developing these debilitating foot problems and associated pain.



Exciting Retatrutide Clinical Trial Results


In a 48-week phase 2 clinical trial for obesity, participants taking 12mg/week of retatrutide lost up to 24% of their starting body weight. All patients on the two highest doses (8mg and 12mg) lost at least 5% of their weight, which is considered clinically meaningful.


In a subset of patients with nonalcoholic fatty liver disease (NAFLD), retatrutide also resolved liver fat content in 9 out of 10 patients after 48 weeks on the two highest doses. This is significant because NAFLD contributes to metabolic disorders like type 2 diabetes.


In a separate 36-week phase 2 trial for type 2 diabetes, retatrutide reduced HbA1c up to 2% from baseline while also causing up to 16.9% weight loss over the 36 week period. This exceeds results seen in most clinical trials for other anti-diabetes medications like semaglutide and tirzepatide.


Based on these dramatic outcomes, experts believe retatrutide has potential to become the most potent weight loss drug on the market upon approval. More importantly, it offers new hope for preventing and relieving foot complications in those living with obesity or diabetes.


Potential Benefits for Foot Pain and Neuropathy


If retatrutide gains FDA approval after phase 3 trials, we expect it could help our patients in the following ways:

  • Alleviating joint pain – Losing excess pounds takes pressure off overburdened, arthritic joints in the ankles, knees, and feet.

  • Preventing neuropathy – Improving blood sugar control helps prevent nerve damage and resulting numbness, tingling, or searing pain.

  • Healing injuries – Healthier weight and blood glucose gives sprains, fractures etc. the best chance to properly heal.

  • Increasing mobility– With less weight burdening their feet, patients often find it easier to remain active and mobile.


While lifestyle modifications are still imperative, retatrutide offers renewed hope for relieving foot pain and neuropathy to keep patients moving.



What’s Next for Retatrutide?


Although phase 2 results are very promising, retatrutide must still complete phase 3 clinical trials and FDA review before becoming widely available to patients.


Phase 3 trials are expected to wrap up in late 2025, after which Eli Lilly will compile all trial data to submit a New Drug Application to the FDA seeking approval. The FDA approval process typically takes 6-10 months from the time of application, meaning retatrutide likely won’t hit the market until 2026 or 2027 if successful.


In the meantime, our team at New Horizon Foot and Ankle Specialists will be following the retatrutide research closely. We specialize in treating patients with diabetes, obesity and related foot conditions causing pain or loss of function. Our comprehensive services include:

  • Routine in-office exams to assess pain, neuropathy, wounds etc.

  • Treatment of foot ulcers, infections, arthritis, and deformities

  • Custom orthotics and prescription footwear to relieve pain

  • Physical therapy and exercises for injury recovery

We always emphasize that lifestyle changes like a healthy diet, regular activity, and diligent foot care must remain the foundation. However, we’re excited at the possibility of new medications like retatrutide providing another tool for protecting foot health and keeping patients active. We hope retatrutide completes trials successfully and gains FDA approval soon to offer renewed hope to our patients.


Key Takeaways

  • Retatrutide shows potential for significant weight loss and HbA1c reduction in phase 2/3 trials

  • Obesity and diabetes substantially increase risk of foot problems like pain and neuropathy

  • By aiding weight loss and glycemic control, retatrutide could help prevent and alleviate foot pain

  • While more research is required, retatrutide provides new hope for improved foot health

  • Lifestyle modifications like diet and exercise remain vital for managing diabetes, obesity, and related foot pain


Frequently Asked Questions


What conditions is retatrutide approved to treat?

Retatrutide is still an investigational drug in clinical trials only. It does not yet have FDA approval for any medical uses.


How much weight loss can it cause?

In phase 2 trials, patients lost up to 24% of body weight over 48 weeks at the highest doses. But results can vary between individuals.


Can it help with my specific foot pain symptoms?

While retatrutide shows promise for foot pain in general, more research is needed on its effects on specific conditions. Please consult your podiatrist.


Does it have side effects?

Like other GLP-1 drugs, retatrutide can cause temporary GI issues like nausea, vomiting, and diarrhea. Safety continues to be evaluated.


When will retatrutide become available?

If phase 3 trials succeed, FDA approval is expected in 2026 or 2027 at the earliest.


Sources:

  1. Eli Lilly and Company. News Release: Lilly's phase 2 retatrutide results published in The New England Journal of Medicine show the investigational molecule achieved up to 17.5% mean weight reduction at 24 weeks in adults with obesity and overweight.

  2. The New England Journal of Medicine. Triple–Hormone-Receptor Agonist Retatrutide for Obesity — A Phase 2 Trial.

  3. Journal of Diabetes Investigation. Glucagon regulates lipolysis and fatty acid oxidation through inositol triphosphate receptor 1 in the liver.

  4. The Lancet. Retatrutide, a GIP, GLP-1 and glucagon receptor agonist, for people with type 2 diabetes: a randomised, double-blind, placebo and active-controlled, parallel-group, phase 2 trial conducted in the USA.

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