Tirzepatide - The Time Has Come

Tirzepatide

PDF version available for printing here - Tirzepatide: The Time Has Come

Possibly the most important trend in improving cardiometabolic health has been the development of safe and effective treatments for insulin resistance and obesity as the root causes for atherosclerosis and early mortality. I am referring to the increased recognition of peptide hormone therapy in promoting wellness, not just the treatment of disease.

The first peptide we will talk about is Tirzepatide, commercially known as Mounjaro and Zepbound for diabetes and obesity, respectively. The prohibitive costs of the brand names and lack of insurance coverage make them unreasonably expensive and out of reach of most of our hands. The use of compounding pharmacies (and other options) makes treating with Tirzepatide extremely reasonable.

I prefer Tirzepatide to Semaglutide (Ozempic, Wegovy) due to its dual mechanism of action and superiority in head-to-head trials. This peptide hormone, composed of 39 amino acids, has both GIP (Glucose-dependent Insulinotropic Polypeptide, also known as Gastric Inhibitory Polypeptide) and GLP-1RA (Glucagon- Like Polypeptide -1 Receptor Agonist) features. 

From the March 6th, 2025, NEJM, pp958, Tirzepatide for Obesity Treatment and Diabetes Prevention," we see a 3-year safety and efficacy trial on this peptide.

Below is a chart on mechanisms of action and why the additional GIP activity of Tirzepatide makes it more efficacious than Semaglutide. The NEJM study now follows 2539 obese people, 1032 also diagnosed with prediabetes in a placebo-controlled trial of 176 weeks active treatment, followed by 17 week non-treatment period. The only thing new in the current trial compared to the original data set (SURMOUNT-1) is a prolonged look at the safety profile especially, as well as the preservation of the weight-loss and diabetes-prevention effects.

So, when I say the time has come, I mean that we have finally found a treatment for the most important metabolic disease of our day. If you have any of the signs of Cardiometabolic Syndrome (sometimes called Syndrome X or Inflammation Syndrome) including increased weight and waist circumference, dyslipidemia especially with low HDL or high triglycerides, elevated blood pressure, and/or elevated insulin, fasting glucose and A1C, then you should consider this treatment.

This trial utilized a dose range of Tirzepatide of 5mg/10mg/15mg given subcutaneous (SQ) weekly. Safety in 3 years was comparable to placebo, especially at the 5mg dosage, which should be adequate for all people who need to lose less than 50 pounds. It could be gradually titrated up, even by 1 mg increments for people who need to lose more weight. I would max out at 10mg.

A newer peptide that might replace Tirzepatide is coming: Retatrutide. This June, 2023, NEJM article, Triple–Hormone-Receptor Agonist Retatrutide for Obesity - A Phase 2 Trial, reviews its triple mechanism of action. It will be more expensive, and I am looking for longer term trials before I can fully endorse this peptide.

I firmly believe with adequate attention to the Foundations of Health and supportive supplementation, people can get to their cardiometabolic goals and dramatically reduce or prevent the use of far more toxic drugs used for lipids, blood pressure, and diabetes. 

Here is an important caveat: we must overcome the idea that this is a “toxic drug” used to treat diabetes. Instead, it is truly a polypeptide hormone that brilliantly helps with feeling full and helping a population of people whose normal signals for metabolic maintenance have been thrown so far askew. Thrown off by stress, and a manipulated food supply– that is another story.

My personal experience by using 5 mg SQ weekly, is that Tirzepatide has helped me lose 25 pounds of weight and maintain that loss. You must remarkably decrease food portions, or you will get nausea and reflux. The nutritional support I recommend beyond the Basic Nutritional Protocol could be extensive, but I have tried to limit it for both convenience and expense. These nutrients will balance and protect you during your journey, furthermore they will eventually allow you to titrate off this peptide hormone therapy.

• Creatine Monohydrate: (Designs for Health, Thorne, others)
  • One scoop = 5 grams creatine, necessary for preservation of muscle mass on this journey. Safe, most effective in women and in those over 50, I still recommend it, with exercise, to help maintain muscle mass during weight loss.
• Muscle Protect with HMB: (Douglas Labs) 
  • With glutamine, BCAAs and the specific BCAA HydroxyMethylButyrate, an important amino acid blend to support muscles and the GI tract. Dose = 1 scoop, approximately 9g total with 1.5 g HMB.
• Fiber Support with both PectaSol-C and SunFiber (TruFiber):
  • PectaSol-C (modified citrus pectin) is an excellent fiber source and daily detoxifier with incredible clinical trials. Dose = 1 scoop (5g) I recommend alternating daily with 1 scoop PectaSol and 1 scoop (7 grams) SunFiber (hydrolyzed guar gum), another fiber superior to psyllium at aiding in detoxification.
• NanoGreens: (BioPharma)
  • As people decrease food intake overall, the need for phytonutrients is rarely met. A dose of ½ - 1 scoop daily of NanoGreens helps prevent multiple nutrient deficiencies.
• Tri-Chromium: (NOW Foods)
  • The need to improve insulin resistance and improve glucose transport into the cell can be aided by this brilliant combination of chromiums. One capsule twice daily provides the correct dose of 1000 mcg chromium daily.
• OptiMag Neuro: (Xymogen)
  • Dosage is 1-2 scoops (200-400 mg elemental Mg) once or twice daily. At least 1-2 scoops in your daily drink. I currently prefer Magnesium L-Threonate as a magnesium supplement as it provides neurological benefits in addition to making sure you keep pooping while on this peptide. Magnesium also improves the efficacy of chromium by improving the insulin resistant condition. If you have another favorite magnesium, please feel free to use it in its place. Goal dosage of 400-800 mg daily, back down for loose stools.
• LiverGB+: (Biocidin Botanicals)
  • A perfectly formulated liver and gallbladder support with milk thistle, artichoke, turmeric and more. At 1 capsule, twice daily, another important part of detoxification while optimizing cardiometabolic health.

To safely and effectively deal with the most important health crisis of our times, an Integral Medicine approach must be taken. The supplements above profoundly improve the metabolic outcomes and safety as we venture into the world or GLP-1RA/GIP peptide hormone therapy. One drink daily, mixing creatine, Muscle Protect, fiber, NanoGreens and OptiMag with 8-12 ounces of water is quite easy (and tastes pretty good!). Adding on the Tri-Chromium and LiverGB+ 1 capsule, twice daily each, also is quite simple.

By providing these nutrients we manage the maintenance of lean body mass, constipation, detoxification and liver support issues not addressed as part of the injection-only approach to weight loss, insulin resistance, and cardiometabolic health. This routine will support you in tapering off the weekly injections as you reach your goals.

Practically speaking, I am utilizing a compounding pharmacy for prescribing to my patients. Currently when I prescribe 2-1 cc vials at 2omg/cc, the cost averages $160 per month. The dosage is 25 units (0.25cc = 5mg) SQ weekly. It is incredibly easy and painless. Honestly, I think I eat so much less that I might be saving money, as I also don’t crave eating out as much. If your doctor won’t prescribe it, you can also find it online without prescription through peptide companies like Peptide Sciences.

Finally, we have something safe, effective and now at a reasonable cost that can help anyone reach their metabolic goals more comfortably. I can tell you personally that not being burdened by hunger as I reach weight goals has been amazing. My wife Miranda will tell you I am almost tolerable to live with! Historically, hunger can make me a bit cranky.

I hope this article allows you to overcome your fears of these easy, safe, weekly, painless injections and let your body more easily align with how you see yourself.

Your Journey to Health and Healing,
Gary E Foresman MD