Weight Loss Drugs Overview

Introduction to Weight Loss Drugs

• Categories of Weight Loss Drugs:
  • Appetite Suppressors: Anorectic that affect neurotransmission.
  • Hormones: Influence metabolism and thermogenesis.
  • Metabolism Targeting: Directly target specific genes.
  • Lower Food Absorption: Impact on signaling pathways.

Historical Context: Rainbow Diet Pills (1940s-1960s)

• Characteristics:
  • Multi-colored pills designed to curb appetite and promote weight loss.
  • Contents included substances like amphetamines, laxatives, and thyroid hormones.

Leptin and Obesity

• Discovery:
  • Jeffrey Friedman identified leptin as a protein-signaling molecule in 1994 from adipose tissue.
  • Functions include regulating metabolism.
  • Absence in mice linked with severe obesity due to defects in leptin or its receptor.
• Mechanism:
  • Crosses blood-brain barrier, reduces food intake, stimulates long-term energy expenditure.
• Clinical Trials:
  • First trials in 1999; effectiveness remained limited but used for lipodystrophy treatment with recombinant methionyl human leptin (r-metHuLeptin).

Cannabinoids and Weight Control

• Cannabinoids:
  • THC is known to stimulate appetite; has 2 receptors.
• CB-1 Antagonists:
  • Reduce weight in animal models; notable case Rimonabant (2005-2007) was linked to reduced BMI and diabetic benefits but caused severe psychiatric side effects.

Opioids and Weight Management

• Opioids:
  • Generally stimulate food intake.
• Antagonists (e.g., Naltrexone):
  • block opioid receptors to reduce appetite; effective in clinical trials but raised concerns over liver toxicity.

Naltrexone/Bupropion (Contrave)

• Approved: 2014.
• Components:
  • Naltrexone: Opioid receptor blocker.
  • Bupropion: Atypical antidepressant affecting mood and appetite.
• Formulation:
  • Extended-release hydrocholoride (8 mg naltrexone / 90 mg bupropion).

Orlistat: A Unique Approach

• Timing: Developed in 1999, based on Lipstatin.
• Mechanism:
  • Targets lipases, prevents triglyceride absorption, inhibits Fatty Acid Synthase (FASN).
• Market Availability:
  • Sold as Alli (OTC in the US) and Xenical (prescription in Canada).

Topiramate

• Usage: Approved since 1996.
• Roles: Appetite suppressor for binge eating, mood enhancer, and anticonvulsant.
• Target: Works on GABA receptors and neurotransmission functions.

Setmelanotide (Imcivree)

• Mechanism: Targets Leptin-Melanocortin pathway as an agonist for MC4R in the brain.
• Impacts: Regulates hunger and satiety; FDA approved in 2020 for specific genetic obesity disorders.

Diabetes Overview

• Types:
  • Group of diseases associated with misregulated blood sugar (hyperglycemia), linked to insulin levels.
  • Symptoms include fatigue, mood changes, and slow healing.

Insulin Discovery

• Key Figures: Banting and Best isolated insulin in 1921, with the first human injection in 1922 leading to a Nobel prize in 1923.
• Function: Produced by pancreatic beta cells; crucial for glucose metabolism, signaling, and energy regulation.

Insulin Mechanism and Signaling

• Insulin Release:
  • High blood glucose stimulates insulin release, which promotes glucose uptake in fat cells and liver regulation.
• Signaling Pathway:
  • Insulin binds to its receptor, activates signaling pathways for glucose metabolism, and regulates various tissue functions.

Diabetes Types and Management

• Type 1 Diabetes:
  • Autoimmune failure of insulin production (5-10% of cases); requires insulin injections or pumps for management.
• Type 2 Diabetes:
  • Insulin resistance (90% of cases); can be managed through diet and lifestyle changes.

Diabetes Medications

• Classes for Type 2:
  • Metformin, Sulfonylureas, DPP-4 inhibitors, SGLT2 inhibitors, Thiazolidinediones, Meglitinides, GLP-1 receptor agonists (e.g., Liraglutide, Semaglutide).

Current Anti-Obesity Drugs (Approved by FDA)

• List of Approved Medications:
  • Bupropion-naltrexone (Contrave)
  • Liraglutide (Saxenda)
  • Orlistat (Xenical, Alli)
  • Phentermine-topiramate (Qsymia)
  • Semaglutide (Wegovy)
  • Setmelanotide (Imcivree).
• Canada's Approved Drugs:
  • Same as above, with explanations on how each drug works to assist obesity management and related conditions.