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Revolutionizing Obesity Treatment: An Introduction To Tirzepatide

Dec 14, 2023
Revolutionizing Obesity Treatment: An Introduction To Tirzepatide

Obesity is a widespread and persistent health issue affecting millions of adults around the world, necessitating effective obesity treatment strategies (1). It’s a condition where a person has too much body fat, and the numbers are staggering. Out of every five adult women, one will face obesity, and for adult men, it’s one out of every seven (2). In the United States alone, nearly 25% of adult deaths are linked to obesity, highlighting the critical need for advanced treatment methods.

Obesity is a complex problem with many causes, making it a chronic condition (3). It’s not just about carrying extra weight; it’s also a big risk factor for serious health problems like diabetes, heart disease, high blood pressure, cancer, and about 200 other diseases. Shockingly, even those with obesity and no other weight-related issues might eventually develop weight-related diseases (3).

But there’s some hope in a medication called Tirzepatide. It’s pretty unique because it tackles obesity in two ways. Think of it as a two-pronged approach. Tirzepatide is the only drug that can connect with both GLP-1 and GIP receptors in your body. This special connection helps lower blood sugar levels, improve insulin sensitivity, make your blood lipid levels healthier, and reduce your body weight by more than 20%.

Tirzepatide got the green light from the U.S. FDA in May 2022, originally to manage type-2 diabetes. But here’s the exciting part: it also got a fast-track ticket from the FDA for adults dealing with obesity or being overweight with weight-related health issues. That means it’s promising news for people looking to tackle obesity and its associated health challenges (4).

Obesity is a Disease

In 2013, the American Medical Association recognized obesity as a disease. Notably, various esteemed organizations and authorities have also acknowledged obesity as a disease, including the American Association of Clinical Endocrinologists, the American Academy of Family Physicians, the American College of Cardiology, the American College of Surgeons, and more (3).

Obesity earns its disease classification for several compelling reasons:

  • Impact on Body Functions: The accumulation of excess body fat disrupts normal bodily functions, clearly meeting the disease definition.
  • Risk Factor for Other Diseases: Obesity substantially increases the risk of other severe conditions like type 2 diabetes, heart disease, cancer, and more (5, 6).
  • Metabolic Abnormalities: Obesity leads to metabolic irregularities such as insulin resistance, chronic inflammation, and hormonal imbalances.
  • Quality of Life: It diminishes mobility, triggers mental health issues, subjects individuals to social stigma, and reduces overall quality of life.
  • Biological and Genetic Factors: Biological and genetic factors play a significant role in excessive hunger, cravings, and how calories are processed in the body.
  • Medical Intervention: Addressing obesity often requires medical intervention, involving lifestyle changes, medication, surgery, and various treatments.
  • Mortality Increase: Obesity is associated with higher mortality rates.

Losing weight can be a daunting challenge, particularly because obesity influences appetite, satiety, metabolism, body fat, and hormonal balance even after weight loss. When individuals with obesity or type 2 diabetes successfully shed 10% of their body weight, they can enjoy a substantial 21% reduction in their cardiovascular disease risk over the following decade compared to those who maintain their weight (3, 5).

Diagnosing Obesity

“Obesity is not a disease which you either do or do not have; rather, it is a continuum, like baldness, in which the diagnosis is made when some arbitrary diagnostic boundary is exceeded (7).”

The most commonly used method for measuring and identifying obesity is the body mass index. This number is calculated by dividing your weight in kilograms by your height in meters squared. In adults, a BMI of ≥30 kg/m2 is defined as obesity. For children and adolescents, different cut-offs are used, depending on age and sex (8).

ClassificationNormalOverweightClass 1 ObesityClass 2 ObesityClass 3 Obesity
Body mass index (BMI)18.0-24.925.0-29.930.0-34.935.0-39.940.0 and higher

Lifestyle-based approaches are the foundation of weight management programs, involving personalized reduced-calorie diets, physical activity, and behavioral counseling. These programs typically result in a 5% to 10% weight reduction. However, only 20% to 40% of people can keep the weight off using diet and exercise.

In the past, surgery was the main effective choice for long-term weight loss, but fewer than 2% of eligible individuals opted for it. Now, guidelines recommend weight-loss medications alongside diet and exercise for anyone with a BMI of 30 or higher or 27 or higher with weight-related medical conditions (6).

How does Tirzepatide work as an obesity treatment?

Type 2 diabetes and obesity are closely linked metabolic conditions, with over 44% of type 2 diabetes cases worldwide associated with excess weight (5). Many medications initially used for managing type 2 diabetes are now repurposed for fat loss treatment.

The pancreas plays a crucial role by producing insulin and glucagon, which regulate blood sugar levels. Insulin helps lower blood sugar by facilitating the entry of glucose into body cells for energy, while glucagon and other hormones increase blood sugar levels.

Incretins are natural hormones released by your body, particularly from the cells lining your small intestine after meals. They prompt the pancreas to release insulin. Two notable incretins are glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP).

Tirzepatide closely resembles your body’s natural GLP-1 and GIP hormones. It encourages the pancreas to release insulin and reduces glucagon release, leading to lower blood sugar levels. Moreover, when tirzepatide attaches to GLP-1 and GIP receptors in the stomach, intestines, and brain, it curbs appetite, diminishes cravings, and slows stomach emptying.

Tirzepatide stands out in treating obesity due to its unique ability to bind to both GLP-1 and GIP receptors (4).

Tirzepatide has the following beneficial effects (4, 9, 10):

  • Suppresses appetite
  • Increases satiety
  • Decreases food cravings
  • Slows food digestion
  • Increases weight loss
  • Increases insulin release from the pancreas
  • Decreases glucagon release from the pancreas
  • Decreases liver fat
  • Protects bone density
  • Protects heart function
  • Increases insulin sensitivity
  • Lowers blood sugar
  • Decreases blood pressure
  • Reduces LDL (bad) cholesterol
  • Increases HDL (good) cholesterol
  • Reduces triglycerides
Picture of a futuristic lab for obesity treatment

Clinical trials and effectiveness of Tirzepatide

Tirzepatide underwent rigorous evaluation for both safety and effectiveness in two extensive sets of clinical trials: the SURPASS trials concentrated on type 2 diabetes treatment, while the SURMOUNT trials were dedicated to tackling obesity. Remarkably, in every instance, tirzepatide delivered substantial reductions in blood sugar levels, hemoglobin A1C (a three-month blood sugar measure), and body weight.

Surmount 1 Clinical Trial

In an extensive 72-week international clinical trial involving 2,539 adults with obesity or overweight having weight-related health conditions but no diabetes, participants received lifestyle counseling, adhered to a low-calorie diet, and engaged in physical exercise. They were randomly assigned to one of three tirzepatide doses (5 mg, 10 mg, or 15 mg) or a placebo. The trial aimed to evaluate tirzepatide’s weight loss potential at each dose. Here are the key findings:

  • Tirzepatide 5 mg: Participants achieved an average 15% reduction in their body weight.
  • Tirzepatide 10 mg: Participants achieved an average 19.5% reduction in their body weight.
  • Tirzepatide 15 mg: Participants achieved an average 21% reduction in their body weight.
  • Placebo: Participants achieved an average 3% reduction in their body weight.

The second study objective was to determine the percentage of participants in each dose group who lost at least 5% of their body weight within 72 weeks (1):

  • Tirzepatide 5 mg: 85% of participants achieved at least a 5% reduction in body weight.
  • Tirzepatide 10 mg: 89% of participants achieved at least a 5% reduction in body weight.
  • Tirzepatide 15 mg: 91% of participants achieved at least a 5% reduction in body weight.
  • Placebo: Only 34.5% of participants achieved at least a 5% reduction in body weight.

Surmount 2 Clinical Trial

In the SURMOUNT 2 clinical trial, which resembled SURMOUNT 1, participants had type 2 diabetes and were currently receiving metformin treatment. Individuals using insulin were not included in the trial due to concerns about potential low blood sugar when combining insulin with tirzepatide. The trial assigned participants randomly to receive either tirzepatide (10 mg or 15 mg) or a placebo. Here are the notable outcomes:

Change in body weight (11):

  • Tirzepatide 10 mg: Participants experienced an average body weight reduction of 12.8%.
  • Tirzepatide 15 mg: Participants experienced an average body weight reduction of 14.7%.
  • Placebo: Participants experienced an average body weight reduction of 3.2%.

Change in hemoglobin A1C (11):

  • Tirzepatide 10 mg: A1C levels decreased by 2.1 percentage points.
  • Tirzepatide 15 mg: A1C levels decreased by 2.1 percentage points.
  • Placebo: A1C levels decreased by 0.5 percentage points.

Surmount 3 Clinical Trial

In this 72-week trial, researchers explored whether tirzepatide could contribute to or help maintain weight loss in individuals who had undergone an intensive diet and exercise program, shedding a minimum of 5% of their body weight. Participants were randomly assigned to either receive tirzepatide or a placebo.

In the initial phase of the trial, participants achieved an average weight loss of 6.9% of their body weight through intensive lifestyle modifications. By week 72, participants receiving tirzepatide experienced an additional 18.4% reduction in their body weight, reaching a total weight loss of 24.3%. Conversely, participants on the placebo regained 2.5% of their body weight (12).

Surmount 4 Clinical Trial

In this extensive 2-year clinical trial, researchers are assessing the effectiveness of tirzepatide in supporting long-term weight maintenance. The trial is divided into two phases. In the initial 36-week phase, all participants were administered tirzepatide. Subsequently, during the second 52-week phase, participants were randomly assigned to receive either tirzepatide or a placebo.

At the conclusion of the initial trial phase, participants achieved a remarkable mean weight loss of 21% over a span of 72 weeks. As the second phase unfolded, individuals who continued with tirzepatide experienced an additional 6.7% reduction in their body weight, summing up to an impressive total weight loss of 26.6% over 84 weeks. Conversely, participants who received the placebo regained 14.8% of their body weight. These findings highlight the significant role of tirzepatide in promoting sustained weight loss (13).

Clinical Trial for obesity treatment

SURPASS-1 Clinical Trial

In this comprehensive 40-week clinical trial, researchers rigorously evaluated the safety and efficacy of tirzepatide in individuals diagnosed with type 2 diabetes, whose blood sugar levels remained inadequately controlled despite dietary and exercise measures. Participants were assigned to receive tirzepatide at varying doses (5 mg, 10 mg, or 15 mg) or a placebo, with the primary focus being the alteration in hemoglobin A1C, a key indicator of blood sugar levels over three months.

Changes in mean body weight were as follows:

  • Tirzepatide 5 mg: Participants exhibited an average body weight reduction of 7.9%.
  • Tirzepatide 10 mg: Participants experienced a noteworthy body weight decrease of 9.3%.
  • Tirzepatide 15 mg: Participants achieved a substantial reduction in body weight, averaging 11%.
  • Semaglutide 1mg: This comparator group displayed a modest body weight decrease, averaging 0.9%.

Regarding the change in hemoglobin A1C over 40 weeks:

  • Tirzepatide 5 mg: A1C levels reduced by 1.87 percentage points.
  • Tirzepatide 10 mg: A1C levels decreased by 1.89 percentage points.
  • Tirzepatide 15 mg: A1C levels declined by 2.07 percentage points.
  • Placebo: A1C levels saw a minimal increase of 0.04 percentage points.

Notably, findings from the SURPASS 1 clinical trial underscore the remarkable effectiveness of tirzepatide in reducing both blood sugar levels and body weight across all dosage levels (13). Impressively, approximately half of all study participants achieved normal blood sugar levels without experiencing episodes of low blood sugar (10).

SURPASS-2 Clinical Trial

In this extensive study, researchers delved into the comparative effectiveness of tirzepatide, semaglutide (another GLP-1 agonist), and metformin in individuals grappling with type 2 diabetes. The study enrolled 1,829 adults whose diabetes management remained suboptimal with metformin alone. These participants were randomly assigned to receive either tirzepatide (at doses of 5 mg, 10 mg, or 15 mg) or semaglutide (at 1 mg) over a span of 40 weeks.

Significant insights emerged regarding changes in mean body weight (9):

  • Tirzepatide 5 mg: Participants exhibited a substantial average body weight reduction of 8.5%.
  • Tirzepatide 10 mg: Participants achieved an impressive average body weight decrease of 11%.
  • Tirzepatide 15 mg: Participants experienced a remarkable average body weight reduction of 13%.
  • Semaglutide 1mg: This comparator group displayed a moderate average body weight reduction of 6.7%.

Likewise, alterations in hemoglobin A1C levels (a vital indicator of blood sugar levels over three months) were scrutinized (9):

  • Tirzepatide 5 mg: A1C levels demonstrated a significant reduction by 2.0 percentage points.
  • Tirzepatide 10 mg: A1C levels displayed a substantial decline by 2.2 percentage points.
  • Tirzepatide 15 mg: A1C levels witnessed a notable decrease by 2.3 percentage points.
  • Semaglutide 1mg: This group registered an appreciable reduction in A1C levels, measuring 1.9 percentage points.

Remarkably, tirzepatide showcased its superiority over semaglutide in promoting both weight loss and the management of hemoglobin A1C levels at dosages of 5 mg, 10 mg, and 15 mg. Furthermore, it’s noteworthy that the weight loss effect did not plateau at any juncture throughout the trial, indicating its sustained efficacy (9).

SURPASS-3 Clinical Trial

In this comprehensive clinical trial, researchers undertook a head-to-head comparison between tirzepatide and insulin degludec in individuals diagnosed with type 2 diabetes whose symptomatic management remained inadequate. Importantly, these participants had never been exposed to insulin therapy. During the three-month period preceding their trial enrollment, they were administered either metformin as a sole agent or metformin in conjunction with an SGLT2 (Sodium/Glucose Transporter 2) medication.

Subsequently, these individuals were randomly allocated to receive either tirzepatide (at dosages of 5 mg, 10 mg, or 15 mg) or insulin degludec (14).

In terms of changes in mean body weight (14):

  • Tirzepatide 5 mg: Showcased a substantial average body weight reduction of 7.5%.
  • Tirzepatide 10 mg: Achieved an impressive average body weight decline of 10.7%.
  • Tirzepatide 15 mg: Elicited a remarkable average body weight reduction of 13%.
  • Insulin degludec: Encountered an average body weight increase of 2.4%.

Similarly, the alterations in hemoglobin A1C levels were assessed (14):

  • Tirzepatide 5 mg: Experienced a significant reduction in A1C levels by 1.9 percentage points.
  • Tirzepatide 10 mg: Demonstrated a substantial A1C decrease by 2.2 percentage points.
  • Tirzepatide 15 mg: Notably achieved a decrease in A1C levels by 2.4 percentage points.
  • Insulin degludec: Registered a decrease in A1C levels by 1.34 percentage points.

This extensive clinical trial unequivocally underscores tirzepatide’s superiority in attaining and maintaining optimal blood glucose levels over a 52-week period when compared to insulin therapy. Impressively, approximately 93% of trial participants who received tirzepatide successfully reached their target hemoglobin A1C levels.

Moreover, the journey toward weight loss commenced as early as four weeks after commencing tirzepatide therapy, with individuals consistently shedding pounds throughout the 52-week study, without encountering a plateau (14).

SURPASS-4 Clinical Trial

In this extensive 52-week clinical trial, tirzepatide underwent a rigorous comparison against insulin glargine in individuals grappling with type 2 diabetes, marked by uncontrolled blood sugar levels while being treated with metformin, sulfonylurea, or SGLT-2 inhibitors, and who harbored a heightened risk of cardiovascular disease. Participants were systematically assigned to receive either tirzepatide (in doses of 5 mg, 10 mg, or 15 mg) or insulin glargine (15).

Regarding the shifts in mean body weight (15):

  • Tirzepatide 5 mg: Demonstrated a commendable average reduction in body weight by 7.1%.
  • Tirzepatide 10 mg: Showed substantial progress, with an average body weight reduction of 9.5%.
  • Tirzepatide 15 mg: Displayed remarkable results, achieving an average body weight decrease of 11.7%.
  • Insulin glargine: Exhibited an average body weight increase of 1.9%.

Furthermore, modifications in hemoglobin A1C levels were meticulously assessed (15):

  • Tirzepatide 5 mg: Marked a substantial decline in A1C levels by 2.24 percentage points.
  • Tirzepatide 10 mg: Evidenced a commendable A1C decrease by 2.43 percentage points.
  • Tirzepatide 15 mg: Notably registered a significant reduction in A1C levels by 2.58 percentage points.
  • Insulin glargine: Presented a decrease in A1C levels by 1.44 percentage points.

Participants embracing tirzepatide experienced significant enhancements in their cardiovascular well-being (15):

  • Reduced systolic and diastolic blood pressure
  • Elevated mean pulse rate
  • Diminished blood triglyceride levels
  • Lowered LDL (bad) cholesterol
  • Heightened HSL (good) cholesterol

Crucially, this study focused on individuals contending with inadequately controlled type 2 diabetes and who faced an elevated risk of heart disease. Impressively, all three tirzepatide dosage levels delivered substantial improvements in glucose management, body weight reduction, and cardiovascular risk profile enhancements (15).

SURPASS 5 Clinical Trial

In this 40-week clinical trial, participants grappling with poorly controlled type 2 diabetes, who were concurrently prescribed insulin glargine (with or without metformin), underwent a rigorous evaluation. They were allocated to receive tirzepatide in varying doses (5 mg, 10 mg, or 15 mg) or were administered a placebo.

Exploring the shifts in mean body weight (16):

  • Tirzepatide 5 mg: Notably, participants achieved an average body weight reduction of 5.4%.
  • Tirzepatide 10 mg: Demonstrated substantial progress, yielding an average body weight decrease of 7.5%.
  • Tirzepatide 15 mg: Impressed with a remarkable average body weight reduction of 8.8%.
  • Insulin glargine: Contrasted by an average body weight increase of 1.6%.

Likewise, alterations in hemoglobin A1C levels were meticulously assessed (16):

  • Tirzepatide 5 mg: Commendably witnessed a substantial A1C decrease by 2.1 percentage points.
  • Tirzepatide 10 mg: Impressed with a commendable reduction in A1C levels by 2.4 percentage points.
  • Tirzepatide 15 mg: Notably demonstrated a significant reduction in A1C levels by 2.3 percentage points.
  • Insulin glargine: Exemplified a decrease in A1C levels by 0.86 percentage points.

Remarkably, this 40-week trial evidenced that participants contending with inadequately managed type 2 diabetes experienced markedly improved blood sugar control and significant weight loss upon incorporating tirzepatide into their regimen (16).

side effects

Potential side effects and precautions of Tirzepatide

Commonly reported side effects of tirzepatide encompass symptoms like nausea, vomiting, decreased appetite, constipation, indigestion, stomachache, and diarrhea. These side effects tend to manifest more prominently during the initial phase of tirzepatide usage or upon dosage escalation. However, many individuals using tirzepatide observe a gradual reduction in these symptoms over time.

It’s noteworthy that tirzepatide can delay stomach emptying, potentially influencing the absorption of other medications.

Predominantly, the most frequently encountered side effects of tirzepatide in clinical trials include (17):

  • Nausea (18%): Managing this effect may involve consuming smaller, frequent meals throughout the day.
  • Diarrhea (17%): Adhering to a low-fat and bland diet can be helpful.
  • Vomiting (9%): Addressing this concern may entail consuming smaller meals consisting of bland foods, with a suggestion to consult your doctor if you struggle to maintain hydration.
  • Constipation (7%): Strategies such as increasing fiber and water intake and incorporating physical activity into your daily routine can assist.
  • Indigestion (5%): Remaining upright for approximately 30 minutes post-meals and avoiding eating within 2 hours of bedtime can be beneficial.
  • Stomach pain (5%): It is advisable to reach out to your healthcare provider if you experience stomach pain.

Moreover, potential serious adverse effects associated with tirzepatide and other GLP-1s encompass (17):

  • Diabetic retinopathy in individuals with type 2 diabetes
  • Gallbladder disease
  • Acute kidney injury
  • Hypersensitivity or allergic reactions
  • Thyroid cancer
  • Injection site reactions
  • Accelerated heart rate
  • Low blood sugar
  • Suicidal behavior or ideation
  • Pancreatitis inflammation
  • Intestinal blockage

Tirzepatide bears a boxed warning concerning the potential risk of thyroid C-cell tumors. This concern arose due to an observed increase in thyroid cancers during rodent testing of tirzepatide. However, it remains uncertain whether tirzepatide poses a similar risk of thyroid cancer in humans.

Indications of thyroid cancer include:

  • The emergence of a new mass or lump in the neck
  • Swallowing difficulties
  • Shortness of breath
  • Persistent hoarseness

It is essential to note that individuals with a personal or family history of medullary thyroid carcinoma or multiple endocrine neoplasia syndrome type 2 (MEN2) should abstain from using tirzepatide. Additionally, tirzepatide has not undergone examination in individuals with a history of pancreatitis, and it is contraindicated for individuals with type 1 diabetes. Pregnant women or those planning to become pregnant should avoid tirzepatide due to its potential to cause fetal harm.

Comparison with other weight-loss treatments

In the United States, there are currently six approved medications for the treatment of obesity, with many more undergoing development and testing.

Traditionally, the most effective weight-loss drugs operated by suppressing appetite through actions in the brain. GLP-1 RAs (such as liraglutide, semaglutide, and the combined medication tirzepatide) work both in the brain and peripheral organs.

These medications function by slowing down stomach emptying, which helps reduce feelings of hunger and appetite. They also stimulate the release of insulin in the pancreas, enhance insulin sensitivity in the liver, and further decrease hunger and cravings by targeting specific areas in the brain.

The U.S. FDA-approved prescription medications for weight loss include:

Orlistat

Your pancreas releases enzymes called lipases, which are delivered into your intestines following meals. These lipases serve to break down fat into its basic components, allowing it to be absorbed into the bloodstream through the intestinal wall. The way lipases function is akin to how detergents work when you apply them to greasy dishes.

Orlistat operates by inhibiting lipases. When fat isn’t broken down, it exits your body undigested through your stool. Orlistat reduces fat absorption by approximately 30%, meaning that roughly 30% of the dietary fat you consume passes through your intestines and is expelled in your stool, without being utilized for energy. This reduction in fat absorption can contribute to weight loss.

However, as you might expect, expelling undigested fat in your stool can result in some side effects. Common side effects associated with Orlistat use encompass:

  • Oily or fatty stools
  • Excessive intestinal gas
  • Increased frequency of bowel movements
  • A sudden and compelling urge to have a bowel movement
  • Challenges in absorbing fat-soluble vitamins like vitamins A, D, E, and K

If you are prescribed Orlistat, your doctor will likely recommend taking multivitamins to help ensure your body receives an adequate supply of these vitamins. Notably, individuals with malabsorption disorders, gallbladder disease, or those who are pregnant or planning to become pregnant should avoid taking Orlistat.

It’s important to note that individuals using Orlistat tend to lose an average of 6.5 to 7.5 pounds per year, making it a less favored option for weight loss (18, 19).

Naltrexone/Bupropion

Contrave is a prescription weight-loss medication that combines two active ingredients: bupropion, which is an antidepressant and a dopamine/norepinephrine reuptake inhibitor, and naltrexone, which is an opioid receptor antagonist. Together, these medications work to regulate reward pathways in the brain and reduce the common cravings associated with addiction and eating behaviors.

When using Contrave, it should be complemented with a low-calorie diet and a structured exercise regimen. There are specific foods that you should avoid while taking Contrave.

Common side effects associated with naltrexone/bupropion include:

  • Nausea
  • Vomiting
  • Indigestion
  • Diarrhea
  • Constipation
  • Abdominal pain
  • Headache
  • Dizziness
  • Agitation
  • Insomnia

However, certain individuals should refrain from taking bupropion/naltrexone. This includes those with uncontrolled high blood pressure, a history of seizures, a history of eating disorders, or individuals undergoing withdrawal from drugs or alcohol. Pregnant women or those planning to become pregnant should also avoid naltrexone/bupropion. Additionally, if you are currently taking monoamine oxidase inhibitors, this combination medication should not be used.

Research has shown that individuals taking bupropion/naltrexone experienced an average weight loss of 11 pounds within a year (18).

Phentermine/Topiramate

Qsymia is a brand name for a combination medication consisting of two active ingredients: phentermine, an appetite suppressant, and topiramate, an anti-seizure medication. This medication is prescribed for the purposes of weight loss and appetite control.

Phentermine operates by increasing norepinephrine and dopamine levels in the brain, effectively suppressing appetite. On the other hand, topiramate is believed to enhance feelings of satiety, reduce appetite, alter taste receptors, and diminish impulsive eating behaviors. When these two medications are combined, they tend to be more effective for weight loss while causing fewer side effects compared to either drug used alone.

Common side effects experienced when taking phentermine/topiramate include:

  • Dry mouth
  • Tingling sensations and numbness
  • Headache
  • Insomnia
  • Mood changes like depression, anxiety, and irritability
  • Attention-related problems
  • Rapid heartbeat or the sensation of a racing heart rate
  • Dizziness
  • Fatigue

It’s important to note that phentermine/topiramate should not be used by individuals with uncontrolled high blood pressure, coronary artery disease, hyperthyroidism, glaucoma, or those who are sensitive to stimulants. Furthermore, this medication is teratogenic, meaning it may cause harm to a developing fetus. Consequently, it should be avoided by pregnant women or those planning to become pregnant.

Additionally, phentermine/topiramate usage in adolescents and young adults has been associated with an increased risk of suicide and suicidal thoughts.

Research has shown that individuals taking phentermine/topiramate can achieve an average weight loss of approximately 14.5 to 19 pounds within a year (18, 19).

Word cloud for metabolism

Liraglutide

Liraglutide, marketed as Saxenda, is an injectable medication used for weight loss. It functions as a GLP-1 receptor agonist, effectively mimicking the appetite-suppressing and blood-sugar-lowering effects of the body’s natural GLP-1 hormone.

Common side effects associated with liraglutide use include:

  • Nausea
  • Diarrhea
  • Constipation
  • Vomiting
  • Injection site reactions
  • Headache
  • Low blood sugar in individuals with type 2 diabetes
  • Indigestion
  • Fatigue
  • Dizziness
  • Abdominal pain
  • Upper abdominal pain

In addition to these side effects, there are several safety considerations when taking liraglutide, including an increased risk for thyroid cancer (as observed in rodent studies), inflammation of the pancreas, gallbladder disease, low blood sugar, a faster heart rate, kidney disease, and an elevated risk of experiencing suicidal thoughts or behaviors.

When compared to a placebo, liraglutide has been shown to reduce calorie intake by approximately 16%. In clinical trials, participants taking liraglutide achieved significantly greater weight loss compared to those taking a placebo or Orlistat.

Across various clinical trials such as Satiety and Clinical Adiposity-Liraglutide Evidence in Individuals With and Without Diabetes (SCALE), SCALE Maintenance, SCALE Diabetes, and SCALE Sleep Apnea, individuals taking liraglutide lost an average of 11 pounds more than those on a placebo. Moreover, approximately 63% of participants lost at least 5% of their body weight during one-year trials, and slightly over one-third achieved a weight loss of 10% (20).

The LEADER clinical trials have also revealed that liraglutide can lower the risk of major cardiovascular events, including heart attacks and strokes, particularly in individuals predisposed to these conditions (21).

Semaglutide

Semaglutide, available under the brand names Ozempic and Wegovy, is an injectable prescription medication initially designed to manage type 2 diabetes. It operates as a GLP-1 receptor agonist, effectively mirroring the actions of the naturally produced GLP-1 hormone in the body.

Semaglutide offers several beneficial effects:

  • Blood sugar reduction
  • Appetite suppression
  • Diminished food cravings
  • Increased feelings of fullness
  • Slowed stomach emptying

Common side effects associated with semaglutide use include:

  • Nausea
  • Vomiting
  • Diarrhea
  • Constipation
  • Abdominal pain
  • Injection site reactions
  • Allergic reactions

Individuals with a personal or family history of medullary thyroid cancer, multiple endocrine neoplasia 2 (MEN2), or a history of pancreatitis should refrain from taking semaglutide. Semaglutide is also not recommended for pregnant individuals or those planning to become pregnant.

When using semaglutide, it’s important to be aware of a heightened risk of developing thyroid cancer (observed in rodent studies), pancreas inflammation, gallbladder disease, low blood sugar, an increased heart rate, kidney disease, and potential suicidal thoughts.

In the STEP clinical trials, participants taking semaglutide experienced an average weight loss ranging from 14.9% to 17.4% of their body weight over a period of 68 weeks. Beyond weight and fat reduction, semaglutide usage led to improvements in various health indicators, including blood pressure, waist circumference, cholesterol and triglyceride levels, and reduced risk of type 2 diabetes (22).

Tirzepatide

Tirzepatide, an injectable weight-loss medication initially designed to manage type 2 diabetes, is a unique combination of glucose-dependent insulinotropic polypeptide (GIP) and GLP-1. It marks the first medication of its kind and functions by replicating the effects of the naturally produced GIP and GLP-1 hormones in the body.

Tirzepatide has undergone extensive testing for the treatment of type 2 diabetes in the SURPASS clinical trials and obesity in the SURMOUNT clinical trials. In 2022, it received approval from the U.S. FDA as an adjunct to diet and exercise for the treatment of type 2 diabetes (4).

Tirzepatide delivers several benefits (23):

  • Slows stomach emptying, reducing hunger
  • Enhances feelings of satiety by acting in critical brain regions
  • Boosts insulin secretion from the pancreas
  • Improves insulin sensitivity in the liver
  • Increases the breakdown of fat
  • Reduces glucagon release

Common side effects associated with tirzepatide use include:

  • Nausea
  • Diarrhea
  • Vomiting
  • Fatigue
  • Headache
  • Low blood sugar
  • Dizziness
  • Nervousness, anxiety, and depression
  • Fast heart rate
  • Allergic reactions
  • Injection site reactions

During the SURMOUNT clinical trials, the group that received the highest tirzepatide dose, 15 mg, in conjunction with lifestyle counseling, achieved remarkable results, with a 20.9% reduction in their body weight over the 72-week trial.

Over half of the participants lost at least 20% of their body weight, and 36% of those taking 15 mg of tirzepatide achieved a reduction of at least 25% (23).

Additionally, ongoing research includes the development of other combination medications such as an amylin/semaglutide combination, Danuglipron—an oral GLP-1 receptor agonist—for obesity treatment, higher-dose Rybelsus, and LY3437943, a triple receptor agonist aimed at addressing obesity.

Revolutionizing Obesity Treatment: An Introduction To Tirzepatide

Tirzepatide dosage and administration

Tirzepatide is typically administered as a weekly subcutaneous (under the skin) injection. The dosing starts at a lower amount and is gradually increased until you reach your maintenance dose. You have flexibility in choosing the time for your tirzepatide injection, and you can take it with or without meals. When injecting, target the fat just beneath the skin in areas such as the abdomen, thigh, or upper arm. To prevent any potential discomfort or issues, it’s advisable to rotate your injection sites with each dose. This helps ensure that the medication is absorbed effectively and reduces the risk of irritation or lumps at the injection sites.

Week Dosage
Weeks 1-42.5 mg Tirzepatide may cause severe hypoglycemia if taken with another GLP-1 or insulin. 

If you miss a dose, inject tirzepatide as soon as possible within four days. If more than four days have passed, skip the missed dose. 
Weeks 5-85.0 mg
If needed: 
Weeks 9-127.5 mg
Weeks 13-1610.0 mg
Weeks 17-2012.5 mg
Weeks 21 and after15.0 mg (maximum dose)

Success stories and testimonials from Tirzepatide users

Based on reviews from Drug.com and WebMD, tirzepatide appears to have mixed feedback from users:

Drug.com Reviews

  • On Drug.com, tirzepatide received an average rating of 8.7 out of 10.
  • Users who reviewed the medication primarily used it as an off-label treatment for obesity.
  • Patients generally reported significant weight loss and manageable side effects.
  • Constipation was a commonly reported side effect.
  • Most users experienced a steady and consistent weight loss, typically ranging between one and two pounds per week.
  • Some users who rated tirzepatide lower reported experiencing significant side effects such as a fast heart rate, dizziness, and severe diarrhea.

WebMD Reviews

  • On WebMD, tirzepatide received an average rating of 3.8 out of 5, although there were only four reviews.
  • One reviewer gave it a 5-star rating for weight loss but mentioned challenges in obtaining the medication due to frequent pharmacy stock shortages.
  • Another reviewer rated tirzepatide at 4.7, with the main issue being diarrhea.
  • The third reviewer rated tirzepatide at 2.7, primarily due to experiencing body pain despite weight loss.
  • The last reviewer gave it a 3.0, mentioning initial side effects like increased sensitivity to touch, sulfur burps, and diarrhea. They were still working on finding the right dosage.

These reviews reflect individual experiences, and the effectiveness and side effects of tirzepatide can vary from person to person. It’s important for individuals considering tirzepatide to discuss its use, potential benefits, and side effects with a healthcare professional. Additionally, any concerns about side effects or difficulties with the medication’s availability should be addressed with a healthcare provider for guidance and potential adjustments to the treatment plan.

Tirzepatide availability and cost

Tirzepatide, which goes by the brand name Mounjaro, has a listed price of $1,023.04 as stated by Eli Lilly.

For those with commercial insurance covering Mounjaro, there’s a chance to join the Mounjaro Savings Card Program, except for government beneficiaries. Qualifying for this card could mean paying as little as $25.00 for either a 1-month or 3-month prescription, with savings capped at $150 per month.

If you have commercial insurance that doesn’t include Mounjaro in its coverage but need a prescription for it, you might be eligible for up to $575 off a 1-month Mounjaro prescription.

These programs are available until December 31, 2023.

As of October 30, 2023, GoodRx lists Mounjaro’s prices in the Midwest ranging from $996.56 to $1,227.

In comparison, Invigor Medical offers tirzepatide at a rate of $87.50 per week.

Frequently asked questions about Tirzepatide and weight loss

What is Tirzepatide?

Tirzepatide, known as Mounjaro, is a newly approved injectable prescription medication designed for type 2 diabetes, obesity, and long-term weight management. The U.S. FDA granted approval in May 2022, under the brand name Mounjaro, for improving blood sugar control in adults with type 2 diabetes, alongside diet and exercise. Eli Lilly and Company is the creator of Mounjaro, and its approval was based on results from the SURPASS clinical trial program, demonstrating substantial enhancements in glycemic control and weight loss among type 2 diabetes patients. Tirzepatide has also received expedited approval from the U.S. FDA for fat loss treatment, backed by the outcomes of the SURMOUNT clinical trials.

How does Tirzepatide work?

Tirzepatide operates as a dual GIP and GLP-1 receptor agonist. It reduces hunger, increases the feeling of fullness, and enhances blood sugar management by mimicking the actions of naturally occurring GIP and GLP-1 hormones. Tirzepatide stimulates insulin production in the pancreas, slows down stomach emptying, curbs appetite, and enhances insulin sensitivity in the liver.

How is Tirzepatide administered?

Tirzepatide is administered through a once-weekly subcutaneous injection just under the skin. The dose is gradually increased during the initial weeks of treatment until reaching a maintenance dose.

What weight-loss results does Tirzepatide produce?

In clinical trials, individuals taking Tirzepatide experienced an average weight loss ranging from 16% to 22.5% of their body weight compared to a placebo over periods spanning six months to one year.

What are the side effects of Tirzepatide?

The most frequent side effects involve mild-to-moderate gastrointestinal symptoms, such as nausea, vomiting, diarrhea, and constipation. These symptoms are typically more pronounced when starting the medication or adjusting the dose.

How much does Tirzepatide cost?

Retail prices for Tirzepatide vary depending on the prescribed dosage, ranging from $900 to $1500 per month. Savings cards and copay assistance programs are available.

Is Tirzepatide safe for long-term use?

Clinical trials for Tirzepatide have extended up to two years, with no major safety concerns identified so far regarding its continued use. However, more long-term data is needed.

Who should not take Tirzepatide?

Individuals with a personal or family history of medullary thyroid cancer, multiple endocrine neoplasia type 2 (MEN2), or a history of pancreatitis should avoid Tirzepatide. This caution extends to pregnant individuals or those trying to conceive. Tirzepatide use also carries additional risks, including an elevated risk of thyroid cancer (as observed in rodent studies), pancreatic inflammation, gallbladder issues, low blood sugar levels, an increased heart rate, kidney concerns, and a potential rise in suicidal thoughts or actions.

How long does it take for Tirzepatide to start working?

Most people typically experience weight loss and improved blood sugar control within 2-4 weeks of initiating Tirzepatide treatment, with noticeable weight loss occurring around 6 to 9 months.

Conclusion: Is Tirzepatide the game-changer in weight loss treatment?

Tirzepatide stands out as a groundbreaking option for weight loss treatment. Among the GLP-1 receptor agonists, it excels in delivering remarkable weight loss outcomes. When weighing the choices between Ozempic, Wegovy, and Mounjaro, it’s crucial to engage in a comprehensive discussion about your weight loss treatment possibilities with your healthcare provider.

Disclaimer
While we strive to always provide accurate, current, and safe advice in all of our articles and guides, it’s important to stress that they are no substitute for medical advice from a doctor or healthcare provider. You should always consult a practicing professional who can diagnose your specific case. The content we’ve included in this guide is merely meant to be informational and does not constitute medical advice.

References

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