Strong trial evidence for lasting weight loss, better blood sugar, fewer heart attacks and strokes, slower kidney decline and lower death rates — but only in people already carrying excess weight, diabetes or heart disease. Digestive side effects are common, a meaningful share of weight lost is muscle, and most benefit disappears within a year of stopping. (Full Review)
| Marker | Target | Why |
|---|---|---|
| HbA1c | 4.8–5.4% | Average blood sugar over ~3 months; primary efficacy marker |
| Fasting insulin | 2–5 µIU/mL | Detects insulin resistance years before glucose rises |
| HOMA-IR | < 1.0 | Calculated index of insulin resistance combining fasting glucose and insulin |
| ApoB | < 80 mg/dL (< 60 if high cardiovascular risk) | Counts all atherogenic particles; better risk marker than LDL cholesterol |
| Triglycerides | < 80 mg/dL | Responds quickly to visceral fat loss and carbohydrate intake |
| hs-CRP | < 0.5 mg/L | Systemic inflammatory tone; falls markedly on treatment |
| ALT | 10–26 U/L (men), 8–22 U/L (women) | Tracks fatty liver improvement |
| Lipase | Within laboratory reference range | Pancreatic enzyme; establishes a baseline before any pancreatitis concern |
| eGFR with cystatin C | > 90 mL/min/1.73 m² | Kidney filtration; falls transiently with dehydration, improves long term |
| Urine albumin-to-creatinine ratio | < 10 mg/g | Earliest sign of kidney injury and a strong cardiovascular risk marker |
| Ferritin | 50–150 ng/mL (with normal inflammatory markers) | Iron stores; absorption is reduced on treatment and intake falls |
| Vitamin B12 | 500–900 pg/mL | Reduced food intake and absorption concerns; deficiency causes irreversible neurological injury |
| 25-hydroxyvitamin D | 40–60 ng/mL | Nutrient status; adequate levels are associated with better treatment response |
| Appendicular lean mass index (DXA) | Stable or increasing over time | The direct measure of the class's most important longevity risk |
| Grip strength (dynamometer) | > 40 kg (men), > 25 kg (women), or stable | Cheap functional proxy for whole-body strength and an independent mortality predictor |
| Resting heart rate and blood pressure | < 65 bpm; < 120/80 mmHg | Blood pressure falls with weight loss and often requires medication reduction; heart rate rises slightly on treatment |
Cadence: Baseline panel before starting, then 4 weeks and 12 weeks during titration, then 6 months, then every 6–12 months indefinitely for as long as the drug is continued. Body composition and strength every 6–12 months; retinal examination at 6 months only with pre-existing diabetic retinopathy.