Of the incretin-based therapies, GLP-1 receptor agonists (GLP-1RAs) directly activate receptors, whereas dipeptidyl peptidase 4 (DPP-4) inhibitors exert their action by preventing degradation of endogenous GLP-1 and GIP 7
Jimena Tatiana Hathaway, M.D., M.P.H., and colleagues said in the JAMA Ophthalmology study they started investigating the association between semaglutide and optic nerve condition, called nonarteritic anterior ischemic optic neuropathy (NAION), after anecdotal clinical experience

Step 1: Define Your Goals Weight Loss Target: Need to lose 20-40 pounds: Semaglutide sufficient (14.9% average loss) Less expensive option works well Compounded semaglutide at $199/month Need to lose 50+ pounds: Tirzepatide preferred (22.5% average loss) Maximum effectiveness important Compounded tirzepatide at $349/month Need to lose 100+ pounds: Tirzepatide strongly recommended May still need bariatric surgery after medication Medication can help even if surgery eventual goal Timeline: Want faster results: Tirzepatide produces weight loss slightly faster But both require 16-20 months for full results No medication produces safe, sustainable rapid weight loss Have time for gradual approach: Either medication works Semaglutide more affordable for extended timeline Step 2: Assess Your Health Status Medical Conditions: Type 2 Diabetes: Both semaglutide and tirzepatide excellent choices Provide blood sugar control plus weight loss May allow reducing other diabetes medications Cardiovascular Disease: Semaglutide proven to reduce heart attacks/strokes (SELECT trial) May be preferred if heart disease history Tirzepatide cardiovascular trial ongoing Thyroid Cancer or MEN 2 History: Absolute contraindication to all GLP-1s Must use non-GLP-1 options (phentermine-topiramate) Gastrointestinal Disorders: GLP-1s may worsen gastroparesis Consider if severe GERD or chronic GI issues Discuss with provider Pregnancy Plans: Do not use GLP-1s if pregnant or planning pregnancy Stop 2 months before trying to conceive Choose non-GLP-1 option or delay treatment Previous Pancreatitis: Relative contraindication to GLP-1s Use with caution, close monitoring May be safer to avoid Current Medications: Insulin or Sulfonylureas: GLP-1s may cause low blood sugar when combined Need to reduce diabetes medication doses Close monitoring required Blood Thinners: GLP-1s safe with anticoagulants No contraindication Psychiatric Medications: Generally compatible with GLP-1s Naltrexone-bupropion may have more interactions Step 3: Evaluate Your Budget What Can You Afford Long-Term

Even with that, however, tolerance varies widely
Many patients find the clinical benefits outweigh the potential drawbacks when properly managed