Introduction
Weight management is a key component of overall health. Being overweight or obese is more than just a matter of appearance; it’s a condition that significantly increases the risk of chronic disease. This information sheet provides an overview of three medicines designed to help with weight loss and improve related health conditions—Tirzepatide, Semaglutide, and Retatrutide.
Health risks of overweight and obesity
Understanding the health risks associated with being overweight underscores the importance of weight management.
a. Cardiovascular Disease
● Obese individuals face a 32% higher risk of coronary artery disease compared to those of normal weight.
● Approximately 75% of hypertension cases are linked to obesity.
b. Type 2 Diabetes
● About 90% of individuals with type 2 diabetes are overweight or obese.
● For every 1-point increase in Body Mass Index (BMI), the risk of diabetes increases by 7%.
c. Cancer Risk
● Obesity is associated with increased risk for at least 13 types of cancer, including breast cancer (postmenopausal), colorectal cancer, endometrial cancer, kidney cancer, liver cancer, and pancreatic cancer.
● In the United States, approximately 40% of all cancers diagnosed are linked to overweight and obesity.
d. Sleep Apnea
● An estimated 70% of individuals with obstructive sleep apnea are obese.
● A 10% increase in body weight increases the risk of sleep apnea sixfold.
e. Osteoarthritis
● For every 5-point increase in BMI, the risk of osteoarthritis increases by 35%.
f. Non-Alcoholic Fatty Liver Disease (NAFLD)
● Prevalence of non-alcoholic fatty liver disease (NAFLD) can reach up to 90% in obese populations.
g. Reproductive Health
● Women: Obesity can cause menstrual irregularities and infertility. Approximately 30% of infertility cases are linked to weight issues.
● Men: Obesity is associated with reduced testosterone levels, affecting fertility and sexual function.
h. Mental Health
● Obese individuals face a 55% increased risk of developing depression over time. A bidirectional relationship exists: individuals with depression have a 58% increased risk of obesity.
i. Mortality and Life Expectancy
● For every 5-point increase in Body Mass Index (BMI) above 25, the risk of premature death increases by 31%.
weight management
Semaglutide, tirzepatide, and retatrutide all belong to the same class of diabetes and weight loss medications, commonly referred to as GLP-1 (glucagon-like peptide-1) agonists. All these drugs affect GLP-1. However, tirzepatide also affects GIP (glucose-dependent insulinotropic polypeptide), while retatrutide affects GLP-1, GIP, and glucagon.
Receptors
● GLP-1 (Glucagon-like Peptide-1): It enhances insulin release, thereby helping to lower blood sugar levels,
and slows gastric emptying, promoting feelings of fullness.
● GIP (Glucose-dependent Insulinotropic Polypeptide): This receptor helps increase insulin secretion after eating,
further supporting blood sugar regulation. It also participates in metabolic processes that promote weight loss.
● Glucagon Receptors: These receptors participate in regulating energy expenditure and promoting lipolysis (fat breakdown). Activating glucagon receptors can increase metabolic rate, which may aid in weight loss.
Remember, being overweight or obese is a chronic condition that often requires long-term medication. Contrary to popular belief, it’s not simply about eating less and exercising more. Often, your body will make it easier to store fat, resist burning fat for energy, mistakenly signal hunger when you’re not actually hungry, and actively resist your weight loss efforts. Using medication to manage weight is not “cheating,” just as taking blood pressure medication to control hypertension is not “cheating.” Yes, if you stop taking your weight management medication, your weight may increase, just as your blood pressure may rise if you stop taking blood pressure medication.
You absolutely must develop healthy eating habits and control calorie intake, ensure you stay active, and get adequate sleep. Consuming sufficient protein is also crucial. You need protein not only to maintain muscle mass, but all your vital organs require significant amounts of it. Aim for about 1 gram of protein per pound of body weight. For this calculation, use your target weight, not your current weight. For example, if you currently weigh 200 pounds but your target/healthy weight is 140 pounds, your daily goal should be 140 grams. If you have any kidney dysfunction, consult your nephrologist or primary care physician for specific daily protein intake recommendations. You must track your protein consumption. Most people significantly overestimate their protein intake. All of this will increase your weight loss success and help you maintain your weight!
I recommend taking these medications for at least 6 months. Your body wants to maintain its current weight. It will strive to keep a weight “set point.” Lowering this set point takes considerable time. If you wish to keep the weight you’ve lost, taking medication for 6 months or longer increases your likelihood of success. During this period, you must also make lasting lifestyle and dietary changes.
Retatrutide
What is retatrutide?
Retatrutide (pronounced Ret-uh-true-tide) is an investigational, once-weekly injection currently being studied for the treatment of obesity and type 2 diabetes. It is a novel peptide that acts as a triple hormone receptor agonist, targeting the glucagon-like peptide-1 (GLP-1), glucose-dependent insulin secretagogue (GIP), and glucagon receptors. By activating all three receptors, retatrutide is designed to provide a greater metabolic benefit than drugs that target only one or two of these pathways.
How does retatrutide work?
①GLP-1 Receptor Activation:
● Increases insulin secretion: Rybelsus stimulates the pancreas to release insulin when blood sugar rises, thereby aiding blood glucose regulation.
● Reduces glucagon secretion: Inhibits the release of glucagon (a hormone that raises blood sugar), thereby helping to better control blood glucose levels.
● Suppresses appetite: Activating GLP-1 receptors in the brain reduces hunger and increases satiety, promoting weight loss.
● Slows gastric emptying: Delays the rate at which food leaves the stomach, helping prevent rapid postprandial blood sugar spikes.
②GIP Receptor Activation:
● Enhances insulin release: GIP synergizes with GLP-1 to stimulate glucose-dependent insulin secretion from the pancreas.
● Improves insulin sensitivity: It enhances the body’s response to insulin, promoting better glucose uptake by tissues.
③ Activation of glucagon receptors:
● Increases energy expenditure: Activating glucagon receptors promotes the breakdown of stored fat (lipolysis) and stimulates heat production (thermogenesis), thereby increasing calorie burning.
● Weight loss: By enhancing lipolysis and energy expenditure, Retaclitide significantly reduces body weight beyond appetite suppression.
● Effects on the liver: While glucagon stimulates hepatic glucose production, Retaclitide’s balanced activation aims to mitigate adverse impacts on blood glucose levels.
Potential health benefits
● Significant Weight Loss: Clinical trials demonstrate that retatrutide achieves substantial weight reduction. Participants lost an average of 24% of their body weight over 48 weeks, outperforming existing weight-loss medications.
● Improved Glycemic Control: Retatrutide effectively lowers blood glucose levels, positioning it as a promising treatment for individuals with type 2 diabetes. Studies show reductions in participants’ glycated hemoglobin (HbA1c) levels, indicating enhanced blood sugar management.
● Enhanced cardiovascular health: The drug is associated with improvements in cardiovascular risk factors, including reduced blood pressure and lipid levels. These changes help lower the risk of heart disease.
● Reduced liver fat: Retatrutide has demonstrated potential to decrease liver fat content, benefiting patients with non-alcoholic fatty liver disease (NAFLD). This effect may help slow the progression of liver-related conditions.
Potential side effects
● Gastrointestinal issues: These symptoms are common and include nausea, vomiting, diarrhea, and constipation. They typically occur early in treatment and may lessen over time.
● Decreased appetite: While reduced appetite may aid weight loss, it can lead to lower food intake, which some individuals may find difficult to manage.
● Potential hypoglycemia: There is a risk of low blood sugar, especially when used with other blood sugar-lowering medications.
● Injection site reactions: Some trial participants reported mild to moderate reactions at the injection site, such as redness or irritation.
● Dizziness and headaches: These symptoms occurred in some trial participants, typically during the body’s adjustment to the medication.
● Potential gallbladder issues: As with other weight-loss medications, significant weight loss increases the risk of gallstones and other gallbladder-related conditions.
● Increased heart rate: Some participants reported accelerated heart rate, which may require monitoring, especially for those with a history of heart disease.
● Skin effects: Significant weight loss may lead to skin laxity and increased wrinkling. This is not unique to GLP-1 medications. Any factor causing substantial weight loss can exacerbate wrinkles and skin laxity, as the underlying supportive structures of the skin are stretched by excess weight. The heavier the initial weight, the more pronounced this effect during weight loss.
● If you experience intolerable nausea or vomiting, revert to your previous dose and wait several weeks before attempting to increase it again. You do not need to reach the maximum dose. If you are losing weight without significant side effects, you may maintain your current dose. If you experience severe constipation or abdominal pain, stop the medication and see your primary care physician (PCP) or go to the emergency department as soon as possible. If you experience neck swelling or difficulty swallowing, see your primary care physician (PCP) or go to the emergency department.
Dosage Guidelines
Retatrutide is administered subcutaneously once weekly. The starting dose is 1 mg or 2 mg weekly, and the dose is increased every four weeks to a maximum of 12 mg weekly. Very few patients require the maximum dose. The optimal dose is the one that achieves weight loss without unacceptable side effects. Dosage is different for each patient.
If you experience unacceptable side effects such as nausea and vomiting, resume your previous dose for one or two weeks before trying a dose increase. If unacceptable nausea or vomiting persists, continue at the dose you can tolerate.