“Let your food be your medicine, and your medicine be your food.” — Hippocrates

Weight Loss:

GLP-1 Receptor Agonists:

 

 

GLP-1 Receptor Agonists (GLP-1 RA)

New medications that are well-tolerated and able to provide substantial, sustained weight loss over the long term are needed. A new class of drugs, glucagon-like peptide 1 receptor agonists (GLP-1 RA) may meet these criteria . 

Weight loss with GLP-1 RAs is thought to be due to improved appetite control and slowed gastric emptying that together reduced food intake. They are also successful at improving blood sugar (glycemic) control by stimulating insulin secretion and inhibiting glucagon secretion that increases blood sugar, without precipitating hypoglycemia. The current FDA approved GLP-1 RAs: semaglutide (Ozempic, Welgovy & Rybelsus) and Liraglutide (Saxenda). In addition, there is tirzepatide (Mounjaro) – a dual glucose-dependent insulinotropic polypeptide (GIP) and GLP-1 RA.

 

Semaglutide

Semaglutide works to provide weight loss by mimicking a hormone naturally made in the body which helps produce more insulin and reduce blood sugar, as well as action on the brain to reduce appetite and increase the sensation of feeling full after eating. It slows the emptying of the stomach that also prolongs feeling satiated after eating. As a result of these actions people eat less, reducing their calorie intake, resulting in weight loss.

 

The 5 STEP trials ( Semaglutide Treatment Effect in People)

Five research studies (the STEP trials) have identified welcome findings regarding the initiation and maintenance of weight loss. Prior to semaglutide, other FDA-approved medications for obesity produced weight losses of only 6 – 19 lbs at 1 year. STEP 1 found that semaglutide increased this amount to 27 lbs, with a mean 14.9% reduction in baseline weight at 68 weeks, compared with 7%−8% for most other medications for obesity. At 68 weeks, more than half of the participants in STEP 1 lost 15% or more of their initial weight, and 30% of participants lost 20% of initial weight. The magnitude of these losses approaches those produced by sleeve gastrectomy. This amount of weight loss also reliably improves cardiovascular risk factors as well as quality of life.

 

Weight loss in diabetic vs non-diabetic patents

While semaglutide does result in meaningful weight loss in overweight/obese patients with and without type 2 diabetes,  the weight loss at 68 weeks appears to be approximately one-third less in those patients with diabetes. Similar findings have been observed with other medications for obesity, including orlistat, naltrexone-bupropion and liraglutide as well as with behavioral interventions.

 

The need for long term use to avoid regaining weight

The STEP 4 study revealed two very important findings, the first demonstrated that patients will lose substantial amounts of weight during the 16-week upward titration period but will not achieve their maximum weight loss until taking the full dose for 1 year. This continued weight loss contrasts the typical plateau that occurs at approximately 6 months with other weight loss medications and behavioral interventions.

The second finding demonstrated a relatively rapid weight regain in participants who discontinued their semaglutide after only 20-weeks, which is common following the termination of other weight loss medications and behavioral interventions. This underscores the need to take these medications on a long-term basis with the recognition that for most individuals obesity is a chronic condition that can be managed by not cured.

However, following the first year of treatment, continued use of semaglutide may not provide continued weight loss at  the often dramatic rate of the first year. However, the studies suggest that maintaining use of the medication will help avoid regaining the weight that may likely occur if the medication is stopped.

 

STEP 5 – Long-term use (two years)

The 2022 STEP 5 trial evaluated, long-term use of semaglutide for two years (104 weeks) in patients without diabetes. At week 104, participants achieved a mean weight loss of 15.2% from baseline – compared to 3% with placebo plus behavioral intervention. This weight loss is comparable to the mean reduction of 14.9% seen at week 68 in the STEP 1 trial of semaglutide.

Weight loss of ≥5%, a threshold widely used to indicate a clinically meaningful response to therapy, was achieved by >75% of participants at 2 years. Moreover, 61.8% of participants lost ≥10% of baseline weight, and over a third of participants achieved at least 20% weight loss at 2 years.

Prior 68-week trials in adults with overweight or obesity have reported numerous healthful improvements with semaglutide. Consistent with these findings, in STEP 5 at 2 years semaglutide improved a range of cardiac risk parameters, including waist circumference, systolic and diastolic blood pressure, HbA1c levels, total cholesterol, low-density lipoprotein cholesterol, very-low-density lipoprotein cholesterol and triglycerides. Together, these results indicate a beneficial effect of treatment on overall patient health. In addition, semaglutide treatment reduced C-reactive protein levels, a marker of systemic inflammation that is known to be elevated in patients with obesity.

Additional outcomes showed that with semaglutide, 80% of participants with prediabetes at baseline reverted to normal blood sugar levels (normoglycemia) by the end of the trial (compared with 37% of those receiving placebo), while 99% of participants with normoglycemia at baseline maintained normoglycemia at the end of the trial (compared with only 86% with placebo). These findings suggest a potential beneficial effect of semaglutide on glycemic status, but whether semaglutide delays or prevents progression to type 2 diabetes requires more research to confirm.

Summary

In the 68-week trials, semaglutide provides reductions in weight, waist circumference, blood pressure and HbA1c that appear to plateau around week 60, while the 104-week trials show that these healthful changes are sustained through 2 years’ treatment.

 

Semaglutide and Special Populations

  • Impaired kidney function – The STEP trials excluded participants with compromised kidney function. However, the prescribing information states that no dose adjustment of semaglutide is recommended for patients with renal impairment.
  • Those with a history of pancreatitis should use this class of medication’s with caution.
  • Patients with personal or family history of thyroid cancer (medullary thyroid carcinoma, or multiple endocrine neoplasia syndrome type 2) should not use this class of drugs. 
  • For more information regarding precautions, read further below.

 

Forms of  Semaglutide:

  • Injectable: (Welgovy) – FDA-approved for weight loss and Type II diabetes only, not for weight loss
  • Oral: (Rybelsus) – FDA-approved for Type II Diabetes only, not for weight loss
  • Sublingual: (compounded generic) – Compounded drugs do not come under FDA approval

 

Injectable Semaglutide: Ozempic & Welgovy

Subcutaneous semaglutide (Ozempic & Welgovy), a GLP-1 receptor agonist FDA approved for adults over 18 y/o with type 2 diabetes, has shown promise for blood sugar control as well as for promoting weight loss in patients both with or without type 2 diabetes. Recent studies using once-weekly 2.4 mg doses of subcutaneous semaglutide for the treatment of overweight/obesity suggest it to be safe and effective.

A recent multi-center, randomized clinical trial published in 2021 evaluated overweight/obese adults who maintained once-weekly treatment for up to 68 weeks with subcutaneous semaglutide. The study subjects experienced sustained weight loss along with significant improvements in waist circumference, systolic blood pressure, and physical functioning.

Weight loss achieved during the study period reached a plateau at week 60 to 68, ultimately resulting in an estimated reduction of 17.4% body weight over the trial. Notably, 86% of participants attained at least 5% weight loss. In contrast, participants who switched back to placebo after 20 weeks gradually regained weight.

Individual counseling sessions are recommended every 4 weeks to help patients adhere to a reduced-calorie diet (500 calorie deficit per day) and increased physical activity is encouraged (i.e. 150 minutes per week of physical activity such as walking).  It is suggested that both diet and physical activity be recorded daily in a diary or with use of a smartphone application for review during counseling sessions.

Dosing of Injectable Semaglutide (Ozempic & Welgovy)

Semaglutide injections should be initiated at a dose of 0.25 mg once weekly and then escalated every 4 week intervals (see dose-escalation schedule) until reaching the maintenance dose of 2.4 mg once weekly. This escalation schedule is designed to minimize side effects, but if a dose increase is not tolerated, the subsequent escalation step can be delayed for another 4 weeks, after which it should be re-escalated until reaching 2.4 mg once weekly. If needed, this re-escalation step can be postponed again, or the escalation can be stopped at a lower maintenance dose where side effects are tolerable. In patients with type 2 diabetes, blood glucose should be monitored.

If a doses missed and the next scheduled dose is more than two days away the dose should be administered as soon as possible. If more than five days have passed, the dose should be skipped and dosing resumed on the scheduled day.

 

 

Oral Semaglutide: Rebelsus

Rybelsus is a pill form of semaglutide FDA approved for adults over 18 y/o with type 2 diabetes that is to be used along with diet and exercise to improve blood sugar and A1C. Semaglutide is not recommended as the first choice of medicine for treating diabetes type II and is not for use in people with type 1 diabetes.

While not FDA approved for weight loss, anecdotal evidence suggests off-label use of oral semaglutide may be very helpful for some to lose weight. 

A 6-month study evaluated 703 adult type 2 diabetics with an average weight of 195 pounds compared daily doses of 7 and 14 mg Rybelsus combined with dietary intervention and exercise. The control group who took a placebo only lost about 3 pounds while some gained weight. Study subjects that that took 7 mg daily lost an average of 5 pounds while those that took 14 mg doses lost an average of 8 pounds. 

Dosing of Oral Rybelsus

    • Rybelsus tablets come in 7 mg or 14 mg strengths. It is taken by mouth on an empty stomach with a sip of plain water (no more than 4 ounces) soon after awakening.
    • After 30 minutes, one can eat, drink, or take other oral medicines For the best effect, it is recommended to eat 30 to 60 minutes after taking semaglutide
    • Do not split, crush, or chew semaglutide tablets, it should be swallowed whole
    • If one misses a dose of semaglutide, skip the missed dose and take the next dose at the regular time. Do not double the dose to catch up.

 

 

Sublingual Semaglutide: Compounded Generic Liquid

Due to the overwhelming popularity of what appears to be a very successful means of losing weight, there has been a great demand for semaglutide treatment. Due to the high cost of these medications and lack of insurance coverage for their off-label use, especially for those without diabetes, demand for an affordable version is strong.

Because there is an extremely low absorption of the oral tablets (less than 1% per the labeling for Rybelsus®) and because many patients prefer to avoid injections when possible, a new a patent-pending compounded
formulation of semaglutide for sublingual administration is now available.

Sublingual semaglutide is a liquid form of semaglutide intended for daily use.  Although being a compounded version of semaglutide, it is not FDA approved but still recommended only for glycemic control as well as for weight loss in adults over 18 y/o,  both with or without type 2 diabetes.

Sublingual semaglutide is to be used along with diet and exercise to improve blood sugar and A1C and facilitate weight loss. Sublingual semaglutide is not recommended as the first choice of medicine for treating diabetes type II and is not for use in people with type 1 diabetes.

More about sublingual semaglutide

This new formulation of sublingual semaglutide is made with Rybelsus tablets and SubMagna SL HMW. SubMagna is an anhydrous, self-emulsifying drug delivery system developed to carry drugs of high molecular weight (HMW) in a sublingual route of administration. This compounding base also has  mucoadhesive properties which increase the contact time of the drug to the lining (buccal mucosa) of the sublingual space under the tongue to enhance absorption. The buccal mucosa contains blood and lymphatic vessels which allow drugs to rapidly and directly be absorbed into the systemic blood stream by means of a venous drainage to the superior vena cava. Research has demonstrated that SubMagna SL HMW is able to deliver semaglutide into and through human gingival and oral tissues.

Dosing of sublingual semaglutide

Dosing  may be individualized based on response to the medication, including side effects and/or effectiveness. The medication should be taken at least 30 min before eating and waiting at least 90 minutes before swallowing.

    • First Month: Place 0.25 ml (0.5 mg) once daily for 1 week, then 0.5 ml (1 mg) once daily thereafter
    • Second Month: Place 0.5 ml (1 mg) once daily
    • Third Month: Place 0.75 ml (1.5 mg) once daily
    • Fourth Month: Place 1 ml (2 mg) once daily therafter

Cost of sublingual semaglutide

The estimated cost for 15 ml of sublingual semaglutide is $185. This amount of 15 ml/month is ample for the first two months but the third and fourth month dose increases may require up to 30 ml, or up to $370/month.

 

Semaglutide – Maintenance of Treatment

Similar to trials of other anti-obesity medications that emphasize the chronicity of obesity, studies of semaglutide identified the need for continuous, prolonged weekly treatment with semaglutide in order to maintain maximal weight loss. It is not recommended as a short term treatment for rapid weight loss.

The significant and sustained weight loss demonstrated with continued semaglutide treatment has also been accompanied by improvement in waist circumference, lipid profiles, and glucose metabolism, all of which are significant cardiovascular risk factors. Sustained weight loss of this magnitude has been shown to improve obesity-related complications including type 2 diabetes.

In patients with diabetes type 2 who are at high risk for cardiovascular disease, semaglutide not only has demonstrated improvement in blood sugar and body weight but it has also been shown to lower the rate of cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke. The superiority of semaglutide in reducing body weight compared with other anti-diabetic medications has been relatively well established by clinical trials.

 

Semaglutide –  Common Side Effects 

Typically with the class of GLP-1 receptor agonists, the most frequently reported adverse events are transient, mild to moderate in severity and gastrointestinal in nature (namely nausea and vomiting, constipation and abdominal pain). These symptoms usually occur only during the initial period when semaglutide is escalated to the target dose. A common effect of GLP-1 receptor agonists is decreased appetite, the primary mechanism for their effectiveness in weight loss. Over one trial period, only a few participants (5.3%) discontinued treatment because of adverse events and those who continued treatment beyond 20 weeks were unlikely to experience significant problems thereafter.

 

Managing Semaglutide Side Effects

Side effects with semaglutide are not uncommon, but are typically transient, associated with dosage increases and only mild to moderate in severity. Side effects are mostly limited to gastrointestinal symptoms such as nausea, vomiting, constipation, or diarrhea. Increasing fiber and water intake for constipation as well as the use of stool softeners can help. For people with vomiting, smaller volumes of food intake, and more frequent meals may be helpful.

Semaglutide Precautions

    • Semaglutide should be used with caution in those who:
    • Have or have had problems with their pancreas or kidneys
    • Have a history of vision problems related to diabetes
    • Are pregnant or plan to become pregnant. It is not known if semaglutide is harmful to an unborn baby therefore one should stop taking semaglutide two months before planning to become pregnant or who are breastfeeding or plan to breastfeed. Breastfeeding is not recommended while taking semaglutide.
    • Drink alcohol. Use of alcohol should be cautious and limited while using semaglutide because it can increase the risk of developing low blood sugar
    • As with other GLP-1 receptor agonists, semaglutide is associated with increases in heart rate of 1 to 4 beats per minute. Pulse rate should be monitored routinely when taking semaglutide, and the medication should be stopped in those with sustained increases. The small mean increase in pulse rate does not appear to adversely affect the heart.

Side effects of semaglutide compared with other weight loss medications

Phentermine-topiramate has been associated with severe cardiovascular outcomes, while orlistat use increases the risk of renal failure and hepatotoxicity. Semaglutide, on the other hand, lowered death from cardiovascular causes by 26% when compared with placebo. Semaglutide does not affect overall renal function and is considered safe for use in patients with mild to moderate renal impairment. Based on these safety findings, semaglutide appears to be a better alternative to other anti-obesity medications currently on the market. It should also be noted that, semaglutide (like other GLP-1 analogs) has a low risk of hypoglycemia.

 

Semaglutide  – Potential for Serious Side Effects

Most people using semaglutide do not have serious side effects, however, they may include:

  • Possible thyroid tumors, including cancer: In studies with rodents, semaglutide caused thyroid tumors, including thyroid cancer but it is not known if semaglutide causes thyroid tumors or cancer in humans. Therefore, individuals with a personal or family history of thyroid cancer or an endocrine system condition called Multiple Endocrine Neoplasia syndrome type 2 (MEN 2) should not take semaglutide.
  • Inflammation of the pancreas (pancreatitis): Pancreatitis may be associated with severe pain in the abdomen that usually persists, with or without vomiting, and may radiate into the back. Based on findings from animal studies, treatment with GLP-1 RAs is contraindicated in patients with a history of chronic or idiopathic acute pancreatitis.
  • Changes in vision: Changes in vision during treatment with semaglutide can occur. A higher incidence of retinopathy complications, including vitreous hemorrhage and blindness, have been reported in patients treated with semaglutide compared with placebo. This is believed to be related to the rapidity and magnitude of glycemic improvement rather than a direct side effect of semaglutide.
  • Low blood sugar (hypoglycemia): Treatment with semaglutide can cause a drop in blood sugar that may become symptomatic, especially if taken with another medicine that can cause low blood sugar, such as a sulfonylurea or insulin. Drinking large quantities of alcohol, not getting enough calories from food, or doing unusually heavy exercise may also lead to low blood sugar. Signs and symptoms of low blood sugar may include: dizziness or lightheadedness, blurred vision, anxiety, irritability or mood changes, sweating, slurred speech, hunger, confusion or drowsiness, shakiness, weakness, headache, fast heartbeat, and feeling jittery. If symptoms occur, one can rapidly raise their blood sugar by eating a quick source of sugar such as table sugar, honey, candy, or drink fruit juice or non-diet soda.
  • Kidney impairment or kidney failure: In the presence of diarrhea and/or vomiting, people who have kidney impairment may become dehydrated which may worsen kidney function. GLP-1 RAs are contraindicated in those with severely impaired renal function.
  • Serious allergic reactions: Serious allergic reactions to GLP-1 RAs is rare. Symptoms of serious allergic reactions, include swelling of the face, lips, tongue, or throat; problems breathing or swallowing; severe rash or itching; fainting or feeling dizzy; or very rapid heartbeat.
  • Gallbladder problems. Gallbladder problems, principally gall stones, ranges in studies between 0.2% and 4.9% in people who take semaglutide. Symptoms of gallbladder problems may include pain in the upper right or mid-abdomen, yellowing of skin or eyes (jaundice), fever, and clay-colored stools.
  • Cardiovascular issues, including tachycardia and arrhythmias, ranged between 1.5% and 9.8% in STEP trials 1–4.

If these symptoms occur, one should call their healthcare provider right away or go to the emergency room

 

Semaglutide – Drug interactions

Drug interactions can change how medications work and may increase the risk for serious side effects. Because it delays stomach emptying after eating, there is the potential for semaglutide to slow the absorption of medications taken orally, including pain medications. There is only limited study of this side effect with semaglutide, but early trials with 1 mg doses of semaglutide have not identified any significant problems.

  • Beta-blocker medications (such as metoprolol, propranolol, or glaucoma eye drops such as timolol) may prevent the fast, pounding heartbeat one would usually feel when their blood sugar falls too low (hypoglycemia). However, other symptoms of low blood sugar, such as dizziness, hunger, or sweating, are not affected by these drugs.
  • Medications that can affect blood sugar, so any change any medications should be reviewed by a doctor or pharmacist as to how the medications may affect blood sugar. Blood sugar may need to be checked regularly and shared with a doctor.

 

.

Liraglutide (Saxenda)

The lack of clinical trial data on switching between liraglutide 3.0 mg and semaglutide 2.4 mg in individuals with overweight or obesity precludes the development of formal evidence-based recommendations.

Liraglutide is a glucagon-like peptide-1 (GLP-1) receptor agonist 97% similar to native GLP-17 which is secreted by intestinal L-cells at the level of the distal jejunum, ileum and colon in response to the ingestion of carbohydrates, lipids and mixed food. It reduces blood sugar levels, inhibits glucagon secretion, increases insulin secretion, suppresses the appetite and calorie intake, retards gastric emptying, and enhances sensitivity to insulin and is effective in the treatment of diabetes.

Because Liraglutide reduces appetite and consequently reduces food ingestion, it enhances weight loss. Possible side effects include nausea, vomiting, diarrhea, constipation, loss of appetite, dyspeptic symptoms, sensation of weakness, injection site reactions (hematoma, irritation, rash) and dizziness.

Liraglutide, is approved for weight management at a 3 mg/day dosage. A 56 week study with liraglutide demonstrated weight losses of 10% body weight in 33% of subjects and 15% body weight of subjects in 14% of subjects. In clinical trials, weight loss with liraglutide was of lesser magnitude and appeared to plateau earlier (at 20 or 40 weeks) compared with semaglutide (plateaus at 60-68 weeks).

A 2022 systematic review of the effects of semaglutide and liraglutide in individuals with obesity or overweight without diabetes concluded that liraglutide and semaglutide therapy both led to clinically relevant (⩾5%) weight loss in 48.2%–88.7% of obese/overweight adults without diabetes. Furthermore, both liraglutide and semaglutide were well-tolerated.

Liraglutide is structurally highly similar to semaglutide with only a few chemical modifications. The once-daily dosing regimen of 3.0 mg liraglutide has been approved by the FDA for the treatment of obesity. However, the once-daily injection regimen can cause physical and financial stress for some adults, so the once-weekly injection model for the GLP-1RAs has been implemented by some.

One study directly compared liraglutide and semaglutide and concluded that semaglutide 0.2 mg once-daily showed superior weight loss compared to liraglutide 3.0 mg once-daily. Other studies also found that semaglutide is more effective in reducing body weight than liraglutide; however, the vast majority of the studies were based on patients with diabetes and weight loss was not the main primary outcome.

 

How the GLP-1 Medications Work

The Incretin Hormone System

These medications are referred to as GLP-1 agonists, meaning that they act on the same receptors in the body as Glucagon-like peptide 1 (GLP-1) and mimics the action of this hormone. GLP-1 is a hormone released from cells in the small intestine and colon in response to food intake. This hormone binds to GLP-1 receptors in the pancreas, stomach lining, kidney, heart, and brain (hypothalamus).

When blood sugar is high, GLP-1 stimulates the pancreas to release insulin that drives blood sugar into the body’s cells where it is used as energy. When blood sugar is low or normal, GLP-1 inhibits glucagon release from the pancreas which blocks the liver from producing more sugar. GLP-1  also slows stomach emptying, and reduces food intake.

GLP-1 agonists promote weight loss primarily by reducing food intake with minimal effects on how the body expends energy. Use of GLP-1 agonists can result in large reductions in hunger and food cravings, increased fullness and satiety, and better control of eating. Studies show that GLP-1 agonists have direct and indirect effects on nerve pathways involved in control of hedonic appetite (the desire to eat driven by pleasure rather than hunger).

 

Conclusions

Based on the effectiveness of these FDA approved GLP-1 receptor agonists, they may offer pharmacological options for overweight and particularly obese patients who might be considering bariatric surgery, which is currently considered the most effective and reliable intervention available for weight management. In comparism, 40% of participants in the semaglutide study trial who took semaglutide for 68 weeks lost 20% or more of their body weight, which approached the level of weight loss seen with sleeve gastrectomy.

It remains important to combine lifestyle modifications such as dietary and physical activity in the treatment of obesity. Dietary modification is fundamental for the long-term management of obesity and includes a variety of dietary interventions, including intermittent fasting, calorie restriction and different macronutrient compositions (e.g. low-fat diets, low-carbohydrates), avoidance of special foods, and following a certain dietary pattern (e.g. Mediterranean diet).

Physical activity is also crucial for successful weight loss, as it can induce energy deficit and preserve lean muscle mass. The American College of Sports Medicine (ACSM) recommends that individuals exercise 150–250 minutes/week, > 150–250 minutes/week, and 200–300 minutes/week to prevent weight gain, achieve weight loss, and maintain weight loss, respectively. Another clinical trial showed that exercise combined with liraglutide was approximately twice as effective as either treatment alone in reducing body weight and body-fat percentage. It was also associated with the improvements in insulin sensitivity, cardiorespiratory fitness, and maintaining a good mood.

The optimal treatment for obesity should be individualized where treatment decisions consider age, coexisting diseases, drug tolerance, and economic and local medical conditions, For example, naltrexone/ bupropion should not be The ideal treatment for obesity should be a highly individualized, personalized medicine. Treatment decisions will consider age, coexisting diseases, drug tolerance, and economic and local medical conditions. For example, naltrexone/ bupropion does not apply to uncontrolled hypertension patients and phentermine/topiramate treated patients should be monitored closely for depression. However, there is no consensus or guidelines to help clinicians make decisions on which drugs to choose.

 

Dual GLP-1 Agents

Tirzepatide (Mounjaro)

Tirzepatide (Mounjaro) is an injectable prescription medication that is used along with diet and exercise to improve blood sugar (glucose) in adults with type 2 diabetes mellitus. It is a dual glucose-dependent insulinotropic polypeptide (GIP) and GLP-1 RA that is FDA-approved for Type II diabetes only, not for weight loss. Mounjaro is dosed in once-weekly, subcutaneous injection dose-escalations, starting with 5 mg, then 10 mg, then up to 15 mg doses over 20 weeks.

 

Weight Loss with Tirzepatide

A 2022 study evaluated the use of Mounjaro in subjects with a mean body weight of 231 lbs, and a mean BMI of 38 at baseline, in which 94.5% of participants had a BMI of 30 or higher. The mean percentage weight loss after 72 weeks was 15%, with 5-mg weekly doses of tirzepatide, 19.5% with 10-mg doses, and 20.9% with 15-mg doses compared to 3.1% with placebo.

The percentage of participants who had weight loss of 5% or more was 85%, 89% and 91% with 5 mg, 10 mg, and 15 mg doses of tirzepatide respectively, compared to 35% with placebo.  The percentage of participants who had weight loss of 20% or more was 50% and 57% of participants in the 10-mg and 15-mg groups, as compared with 3% in the placebo group.

Side Effects with Tirzepatide

The most common side effects with tirzepatide are nausea, vomiting and diarrhea, mild to moderate in severity, occurring primarily during dose escalation. Side effects cause treatment discontinuation in 4.3%, 7.1%, 6.2%, of participants receiving 5-mg, 10-mg, and 15-mg tirzepatide doses respectively compared to 2.6% with placebo. Hypoglycemia has been reported in <2% of patients taking tirzepatide.

Tirzepatide vs Semaglutide

A 2021 study comparing tirzepatide and semaglutide concluded that tirzepatide at all doses was superior to semaglutide with weight reductions  and improvement of hemoglobin A1c greater with tirzepatide than with semaglutide.

 

 

Resources

Resources for Help

 

References

Appetite Suppressants

  1. Appetite Suppressants – OTC
  2. Appe-control and Hunger Block

 

Appetite Suppressants – Rx

  • Adipex (Phentermine)
  • Belviq (Lorcaserin)
  • Bupropion
  • Contrave (Bupropion/Naltrexone)
  • Invokana (Canagliflozin)
  • Naltrexone
  • Orlistat (Xenical, Alli)
  • Qsymia (Phentermine and Topiramate)
  • Saxenda (Liraglutide)
  • Topamax (Topiramate)
  • Wegovy (Semaglutide)

 

Appetite Suppressants – GLP-1 Receptor Agonists (RA)

GLP-1 RA –  Semaglutide

  1. Semaglutide Medications – Information
  2. Ozempic Information
  3. RYBELSUS Information
  4. Wegovy Information
  5. Effect of Continued Weekly Subcutaneous Semaglutide vs Placebo on Weight Loss Maintenance in Adults With Overweight or Obesity – PMC – 2021
  6. Review Wegovy (semaglutide)- a new weight loss drug for chronic weight management – 2022
  7. Once-Weekly Semaglutide in Adults with Overweight or Obesity – 2021
  8. Once-Weekly Semaglutide in Adults with Overweight or Obesity – PubMed – 2021
  9. Effect of semaglutide and liraglutide in individuals with obesity or overweight without diabetes- a systematic review – 2022
  10. GLP-1-Medications-Article-References-and-PubMed-Links
  11. Sublingual Semaglutide Supportive deposition
  12. The Impact of GLP1 Agonists on Bone Metabolism: A Systematic Review.- 2022
  13. Efficacy and safety of dulaglutide 3.0 and 4.5 mg in patients aged younger than 65 and 65 years or older: Post hoc analysis of the AWARD‐11 trial – 2021
  14. Safety of Semaglutide – 2021
  15. Semaglutide for the treatment of overweight and obesity_ A review – 2023
  16. Two-year effects of semaglutide in adults with overweight or obesity_ the STEP 5 trial 2022
  17. Semaglutide for the Treatment of Obesity – 2021

 

Dual GLP-1 RA Agents

Dual Agent – Tirzepatide (Mounjaro)

  1. Tirzepatide Once Weekly for the Treatment of Obesity – PubMed – 2022
  2. Effects of Tirzepatide, a Dual GIP and GLP-1 RA, on Lipid and Metabolite Profiles in Subjects With Type 2 Diabetes – PubMed – 2022
  3. Tirzepatide versus Semaglutide Once Weekly in Patients with Type 2 Diabetes – PubMed – 2021

 

Liraglutide (Saxenda)

 

 

 

Emphasis on Education

 

Accurate Clinic promotes patient education as the foundation of it’s medical care. In Dr. Ehlenberger’s integrative approach to patient care, including conventional and complementary and alternative medical (CAM) treatments, he may encourage or provide advice about the use of supplements. However, the specifics of choice of supplement, dosing and duration of treatment should be individualized through discussion with Dr. Ehlenberger. The following information and reference articles are presented to provide the reader with some of the latest research to facilitate evidence-based, informed decisions regarding the use of conventional as well as CAM treatments.

 

For medical-legal reasons, access to these links is limited to patients enrolled in an Accurate Clinic medical program.

 

Should you wish more information regarding any of the subjects listed – or not listed –  here, please contact Dr. Ehlenberger. He has literally thous
ands of published articles to share on hundreds of topics associated with pain management, weight loss, nutrition, addiction recovery and emergency medicine. It would take years for you to read them, as it did him.

 

For more information, please contact Accurate Clinic.

 

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