Browse the evidence

Discontinuation of incretin analogues (semaglutide, tirzepatide) leads to significant weight regain, with patients recovering approximately two-thirds of lost weight within one year.

If you stop taking semaglutide or tirzepatide, you will likely regain about two-thirds of the weight you lost within a year. This is because the medication's appetite-suppressing effects wear off. To maintain your weight loss, you likely need to continue the medication long-term under medical supervision.

GLP-1 receptor agonists (GLP-1 RAs) such as semaglutide and tirzepatide can achieve weight loss comparable to sleeve gastrectomy in selected patients, but are limited by real-world factors like cost, tolerability, and adherence.

GLP-1 medications like semaglutide and tirzepatide are highly effective for weight loss, often achieving 15-20% body weight reduction. However, success depends on continuous use; stopping the medication often leads to weight regain. Managing side effects through gradual dosing and addressing cost/access are key to long-term success.

GLP-1 receptor agonists provide renal benefits, including reduced albuminuria and slower eGFR decline, in patients with type 2 diabetes and chronic kidney disease, independent of glycemic control.

If you have type 2 diabetes and chronic kidney disease, GLP-1 RAs like semaglutide can protect your kidneys by reducing albuminuria and slowing the decline of kidney function, even independent of their glucose-lowering effects. Discuss these benefits with your doctor, especially if you are already on other kidney-protective medications.

GLP-1 receptor agonists (semaglutide, tirzepatide, survodutide, retatrutide) promote resolution of metabolic dysfunction-associated steatohepatitis (MASH) and improve liver fibrosis in patients with MASLD/MASH.

If you have MASH or MASLD, GLP-1 RAs like semaglutide and tirzepatide can significantly improve liver health, resolving MASH in many patients and improving fibrosis. These benefits are in addition to their weight loss and cardiovascular benefits. Discuss these options with your liver specialist or primary care provider.

Semaglutide (1.0 mg once weekly) significantly improves physical quality of life (SF-36v2 PCS) in patients with schizophrenia and obesity, with the effect exceeding the minimally important difference, although this improvement is not statistically mediated by weight loss.

If you have schizophrenia and are overweight, semaglutide (1.0 mg weekly) can significantly improve your physical quality of life, such as mobility and physical functioning. This benefit is clinically meaningful and exceeds the threshold for what patients consider important. However, do not expect this medication to directly reduce psychiatric symptoms like hallucinations or negative symptoms, nor does it necessarily improve mental well-being (MCS). The improvement in physical QoL is not solely due to weight loss, suggesting the drug has other beneficial effects. Adherence to the weekly injection is key to achieving these physical health benefits.

Orforglipron reduces systolic blood pressure and atherogenic lipids (LDL, VLDL, triglycerides) with high consistency (low heterogeneity) across doses, suggesting a mechanism independent of weight loss alone.

For cardiovascular health, you may not need the highest dose of Orforglipron. Lower doses (12-24 mg) are sufficient to significantly improve blood pressure and cholesterol levels, while higher doses are needed for maximum weight loss. This allows for a personalized dosing strategy.

Combination therapy of semaglutide and cagrilintide (CagriSema) produces weight loss comparable to multi-receptor agonists by targeting complementary metabolic pathways.

Taking semaglutide and cagrilintide together (CagriSema) is a highly effective strategy for weight loss, performing similarly to newer triple-agonist drugs. It involves two weekly injections. Like other drugs in this class, you may experience gastrointestinal side effects initially, which usually improve over time.

Dual GIP/GLP-1 receptor agonists (tirzepatide) demonstrate enhanced efficacy compared to single GLP-1 agonists, likely due to synergistic modulation of GIP and GLP-1 pathways.

Tirzepatide is a dual-acting drug (GIP and GLP-1) that is more effective than single-acting GLP-1 drugs like semaglutide. It is taken once weekly. You will likely experience gastrointestinal side effects initially, which usually improve over time.

GLP-1 receptor agonists (liraglutide, semaglutide) reduce body weight and improve metabolic parameters by modulating central appetite pathways and delaying gastric emptying.

GLP-1 drugs like semaglutide and liraglutide help you lose weight by reducing appetite and slowing digestion. They are taken daily or weekly. Gastrointestinal side effects are common initially but usually improve.

Tirzepatide treatment in individuals with obesity and prediabetes attenuates the decline in creatinine-cystatin C-based estimated glomerular filtration rate (eGFR) and reduces urine albumin-to-creatinine ratio (UACR) compared to placebo over 176 weeks.

If you have obesity and prediabetes, treatment with tirzepatide (a once-weekly injectable medication) has been shown to help protect your kidney function over a 3-year period compared to placebo. This protection is seen as a slower decline in kidney filtration rates and a reduction in albumin in the urine, even if your kidney function is currently normal. This suggests that early intervention with this medication may offer long-term organ protection beyond just weight loss.

Tirzepatide (all doses) provides statistically greater improvements in triglycerides and diastolic blood pressure compared to Liraglutide, and generally comparable improvements in other cardiometabolic parameters compared to Semaglutide.

Tirzepatide not only aids weight loss but also offers statistically greater improvements in triglycerides and diastolic blood pressure compared to Liraglutide, with generally comparable benefits to Semaglutide for other heart health markers.

GLP-1 receptor agonists provide additive kidney benefits when used in combination with SGLT2 inhibitors, addressing residual cardiorenal risk.

If you are already taking an SGLT2 inhibitor for your kidney and heart health, ask your doctor if adding a GLP-1 receptor agonist could provide additional protection. These medications work through different mechanisms and can offer additive benefits, especially if you still have residual risk factors like high blood pressure or albuminuria.

Incretin therapies (semaglutide, tirzepatide) achieve MASH resolution and fibrosis improvement primarily through substantial, dose-dependent weight loss.

Semaglutide (2.4 mg weekly) and tirzepatide are weekly injections that reduce liver fat and inflammation by driving significant weight loss. They are highly effective for MASH resolution.

Emerging weight-lowering drugs (GLP-1/GIP/Glucagon agonists, amylin analogues, activin receptor antagonists) reduce cardiovascular risk factors (blood pressure, lipids, inflammation) and major adverse cardiovascular events (MACE) in obese patients, with some effects being independent of weight loss.

If you are obese and have cardiovascular risk factors, emerging drugs like semaglutide and tirzepatide offer significant benefits beyond just weight loss, including reduced risk of heart attacks and strokes. These benefits may come from direct effects on blood vessels and inflammation, not just weight loss. While side effects like nausea are common, they can often be managed. Oral options are becoming available, reducing the need for injections. These drugs are most effective when combined with lifestyle changes, but they can provide substantial help where lifestyle alone has failed.

Combining gut hormone analog medications (e.g., GLP-1/GIP agonists) with naltrexone-bupropion extended-release (NB-ER) provides a mechanistic rationale for improved weight loss in patients who fail to achieve goals with monotherapy, by targeting distinct satiety and reward pathways.

If you are taking a GLP-1 medication (like semaglutide or tirzepatide) and hitting a plateau or struggling with food cravings despite following the dose, ask your doctor about adding NB-ER (naltrexone-bupropion). This combination targets both physical fullness and the brain's reward system, which may help you lose more weight than the single medication alone.

Gut hormone analog medications (liraglutide, semaglutide, tirzepatide) reduce energy intake and alter food preferences primarily through delayed gastric emptying and hypothalamic/brainstem satiety signaling, rather than direct effects on reward centers.

GLP-1 medications like semaglutide work mainly by slowing digestion and signaling fullness to the brain, leading to significant weight loss (up to 21% for tirzepatide). While they may help with cravings, this is likely a secondary effect of weight loss rather than a direct 'craving blocker' action.

NB-ER (naltrexone-bupropion extended-release) reduces food cravings and improves control over eating by acting on central hypothalamic and mesolimbic dopaminergic systems, distinct from the peripheral effects of gut hormone analogs.

NB-ER helps with weight loss by targeting the brain's reward system to reduce cravings and improve self-control, rather than just slowing digestion. It typically leads to 6-12% weight loss over a year, depending on whether you have diabetes.

Tirzepatide is associated with significantly greater lean body mass (LBM) loss compared to semaglutide during routine care, with excess relative LBM losses of 1.1% to 2.0% at 3, 6, 9, and 12 months respectively.

If you are taking tirzepatide, expect to lose more lean muscle mass than if you were taking semaglutide for the same amount of weight loss. This effect increases with higher doses and longer duration. To counteract this, prioritize resistance training and adequate protein intake, and monitor your body composition, not just scale weight.

Incretin therapies reduce Major Adverse Cardiovascular Events (MACE) and all-cause mortality in patients with T2DM and/or established cardiovascular disease, independent of glycemic control.

If you have heart disease or high risk, these drugs offer significant protection against heart attacks and death, separate from weight loss. This benefit is a key factor in their clinical value and reimbursement decisions.

Next-generation incretin-based therapies (GLP-1 and GLP-1/GIP receptor agonists) significantly reduce systolic blood pressure, with the majority of this effect mediated by weight loss, though direct tissue-specific mechanisms also contribute.

If you have high blood pressure and obesity or type 2 diabetes, GLP-1 based medications like semaglutide or tirzepatide can significantly lower your blood pressure. Most of this benefit comes from the weight loss these drugs cause, but they also have direct positive effects on your blood vessels and kidneys. While they are more expensive than standard blood pressure pills, they offer broader cardiovascular protection. Discuss with your doctor if you are a candidate, especially if you have resistant hypertension or high cardiovascular risk.

GLP-1/GIP receptor co-agonists may provide cardiovascular protection and slow the decline of kidney function in individuals with type 2 diabetes.

GLP-1/GIP receptor co-agonists may be considered for patients with type 2 diabetes at risk for cardiovascular and kidney issues.

Tirzepatide may provide additional benefits beyond glycemic control for T2DM patients.

Tirzepatide may be beneficial for T2DM patients in ways beyond just lowering blood sugar.

GLP-1 agonists may provide additional benefits beyond weight loss and diabetes management.

Providers should explore the broader implications of GLP-1 agonists for patients with various conditions.

Combining GLP-1 RAs with EBTs may yield synergistic effects.

Practitioners may explore combination therapies for enhanced weight loss outcomes.