How today’s anti-obesity medicines arrived – how effective each is, how they work, what they mean for the kidney, and how they fit in time.
Educational timeline — not individualized advice. It maps US FDA milestones and pivotal-trial efficacy to show how the field developed. Weight-loss figures come from separate trials with different populations — not head-to-head comparisons; where possible the estimand is named so numbers are comparable. Safety and kidney notes are brief label-based summaries, not a substitute for the full prescribing information. Selections made in this timeline are not stored.
Pattern 1 — incretin repurposingSeveral incretin-based agents were first approved for type 2 diabetes, then for chronic weight management — usually under a new brand, and for liraglutide and semaglutide at a higher dose (Victoza→Saxenda, Ozempic→Wegovy). Tirzepatide is an exception: Mounjaro and Zepbound share the same dose range, up to 15 mg weekly.
Pattern 2 — changing mechanisms (a simplified view)Earlier obesity drugs were sympathomimetic or serotonergic; several were later withdrawn for drug-specific safety signals — valvular disease and pulmonary hypertension (the fenfluramines), excess cardiovascular events (sibutramine), or a cancer signal (lorcaserin). The FDA-approved incretin era began with liraglutide 3.0 mg in 2014, with a steep rise in efficacy and, lately, kidney and cardiovascular outcomes.
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1959
Phentermine Ionamin / Adipex-PoralObesity approval
First sympathomimetic anorectic; short-term use only.
Typical weight loss: ~3-4 kg vs placebo, short-term (pooled RCTs)
Approved: 1959
Class: Sympathomimetic amine
Mechanism: Sympathomimetic · oral
Approved as a short-term (a few weeks) adjunct to diet. Related older agents: diethylpropion (Tenuate, 1959), benzphetamine (Didrex, 1960), phendimetrazine (Bontril).
Kidney considerations: Limited CKD data; sympathomimetic load raises BP/heart rate. Caution in reduced eGFR and cardiovascular disease.
Safety: Raises blood pressure and heart rate; avoid in cardiovascular disease, uncontrolled hypertension, hyperthyroidism, or with MAOIs. Schedule IV (benzphetamine and phendimetrazine are Schedule III).
1973
Fenfluramine PondiminoralWithdrawn
Serotonergic appetite suppressant – later half of “fen-phen.”
Approved: 1973
Class: Serotonergic
Mechanism: Serotonergic / monoamine · oral
Approved 1973; used off-label with phentermine as “fen-phen” in the 1990s. Note: fenfluramine returned to the US market in 2020 as Fintepla for seizures in Dravet and Lennox-Gastaut syndromes, under a REMS with echocardiographic monitoring – not as a weight-loss drug.
Safety: Withdrawn 1997 for valvular heart disease and pulmonary hypertension.
Source: FDA historical / post-market safety archive
1996
Dexfenfluramine ReduxoralWithdrawn
Serotonergic appetite suppressant.
Approved: Apr 1996
Class: Serotonergic
Mechanism: Serotonergic / monoamine · oral
Approved April 29, 1996; on the market barely a year before the valvular-disease signal emerged.
Safety: Withdrawn September 1997 for valvular heart disease.
Source: FDA archive / contemporaneous reporting
1997
Fen-phen withdrawn fenfluramine + dexfenfluramineoralWithdrawn
Pulled September 15, 1997 for valvular heart disease.
Approved: Sep 1997
Class: Serotonergic
Mechanism: Serotonergic / monoamine · oral
FDA requested withdrawal of both fenfluramine and dexfenfluramine after reports of valvular heart disease and pulmonary hypertension – a landmark safety event for the field.
Source: FDA post-market drug safety archive
1997
Sibutramine MeridiaoralWithdrawn
SNRI appetite suppressant (later withdrawn 2010).
Approved: Nov 1997
Class: Serotonin-norepinephrine reuptake inhibitor
Mechanism: Serotonergic / monoamine · oral
Approved November 1997. Withdrawn in 2010 after the SCOUT trial showed excess cardiovascular events.
Safety: Raised blood pressure and heart rate; withdrawn 2010 for excess non-fatal MI and stroke.
1999
Orlistat (Rx) XenicaloralObesity approval
First non-centrally-acting agent: a gut lipase inhibitor.
Typical weight loss: ~3-4% drug-attributable (placebo-subtracted); ~10% total incl. lifestyle (XENDOS, 1 yr)
Approved: Apr 23, 1999
Class: Lipase inhibitor
Mechanism: Lipase inhibitor · oral
120 mg three times daily with meals. Blocks ~30% of dietary fat absorption; acts locally in the gut, not on appetite.
Kidney considerations: Rare oxalate nephropathy / acute oxalate-induced AKI; caution in CKD and in calcium-oxalate stone-formers.
Safety: GI/steatorrhoea; fat-soluble vitamin (A,D,E,K) malabsorption; rare severe liver injury.
Source: FDA approval letter, NDA 020766
2007
Orlistat (OTC) AllioralObesity approval
First OTC weight-loss drug (60 mg).
Approved: Feb 7, 2007
Class: Lipase inhibitor
Mechanism: Lipase inhibitor · oral
Half-strength orlistat approved for over-the-counter use in overweight adults ≥18 with a reduced-calorie, low-fat diet.
Kidney considerations: Same oxalate-nephropathy caution as prescription orlistat.
Safety: GI effects; fat-soluble vitamin malabsorption.
Source: Drugs@FDA label, NDA 021887
2010
Liraglutide VictozainjectableDiabetes
First once-daily GLP-1 for type 2 diabetes (1.8 mg).
Approved: Jan 25, 2010
Class: GLP-1 receptor agonist
Mechanism: GLP-1 agonist · injectable
Approved for glycemic control in type 2 diabetes – four years before its obesity twin. (Exenatide/Byetta, 2005, was the first GLP-1 receptor agonist; liraglutide was the first once-daily one.)
Kidney considerations: No dose adjustment for renal function; watch volume depletion / prerenal AKI with GI losses.
Safety: Boxed warning: thyroid C-cell tumours (contraindicated with personal/family history of medullary thyroid carcinoma or MEN 2). Pancreatitis, gallbladder disease; not in pregnancy.
Source: FDA approval history, NDA 022341
2010
Sibutramine withdrawn MeridiaoralWithdrawn
Withdrawn for cardiovascular events (SCOUT).
Approved: Oct 2010
Class: SNRI
Mechanism: Serotonergic / monoamine · oral
FDA requested withdrawal in October 2010; formally withdrawn later that year based on excess non-fatal MI and stroke.
Source: Federal Register, Dec 21, 2010
2012
Lorcaserin BelviqoralWithdrawn
5-HT2C agonist (later withdrawn 2020).
Approved: Jun 27, 2012
Class: Selective 5-HT2C agonist
Mechanism: Serotonergic / monoamine · oral
Approved June 27, 2012; withdrawn February 2020 after a safety trial found a numerically higher cancer incidence.
Safety: Withdrawn 2020 over a cancer signal in a long-term safety trial.
Source: FDA approval letter, NDA 022529
2012
Phentermine / topiramate ER QsymiaoralObesity approval
First modern combination for chronic weight management.
Typical weight loss: -9.8 to -10.9% total; ~9 pts vs placebo (EQUIP / CONQUER, 56 wk)
Approved: Jul 17, 2012
Class: Sympathomimetic + antiepileptic (combination)
Mechanism: Combination · oral
Approved for adults with BMI ≥30 (or ≥27 with a comorbidity). Later expanded to adolescents ≥12 in June 2022.
Kidney considerations: Topiramate causes calcium-phosphate nephrolithiasis and a non-anion-gap metabolic acidosis (carbonic-anhydrase inhibition); caution in CKD; avoid combining with other carbonic-anhydrase inhibitors.
Safety: Teratogenic – topiramate raises oral-cleft risk; dispensed under a REMS with required contraception. Increased heart rate, cognitive/mood effects; avoid in glaucoma, hyperthyroidism, and with MAOIs.
2014
Naltrexone / bupropion ER ContraveoralObesity approval
Opioid-antagonist + antidepressant combination.
Typical weight loss: -6.1% total; -4.8 pts vs placebo (COR-I, 56 wk)
Approved: Sep 10, 2014
Class: Opioid antagonist + aminoketone
Mechanism: Combination · oral
Approved for chronic weight management in adults (BMI ≥30, or ≥27 with a comorbidity) with diet and exercise.
Kidney considerations: Maximum one tablet twice daily if eGFR is below 60; not recommended in end-stage kidney disease.
Safety: Boxed warning: suicidal thoughts/behaviours (bupropion). Contraindicated in uncontrolled hypertension, seizure disorder, bulimia/anorexia, chronic opioid use, and with MAOIs.
Source: Drugs@FDA, NDA 200063
2014
Liraglutide SaxendainjectableObesity approval
First GLP-1 approved for obesity (3.0 mg).
Typical weight loss: -8.0% total; -5.4 pts vs placebo (SCALE, 56 wk)
Approved: Dec 23, 2014
Class: GLP-1 receptor agonist
Mechanism: GLP-1 agonist · injectable
Same molecule as Victoza, at a higher dose and new brand for chronic weight management – the template for the diabetes→obesity pattern.
Kidney considerations: No renal dose adjustment; watch dehydration / prerenal AKI with nausea and vomiting.
Safety: Boxed warning: thyroid C-cell tumours (MTC/MEN 2 contraindication). Pancreatitis, gallbladder disease; not in pregnancy.
Source: FDA approval history
2017
Semaglutide OzempicinjectableDiabetes
Once-weekly GLP-1 for type 2 diabetes.
Approved: Dec 5, 2017
Class: GLP-1 receptor agonist
Mechanism: GLP-1 agonist · injectable
Weekly injection; the 2 mg dose was added in March 2022. Precursor to Wegovy, and the molecule later shown to protect the kidney (FLOW, 2024/2025).
Kidney considerations: No renal dose adjustment; later gained a dedicated CKD indication (see 2025).
Safety: Boxed warning: thyroid C-cell tumours (MTC/MEN 2 contraindication). Pancreatitis, gallbladder disease.
Source: FDA approval history, NDA 209637
2019
Semaglutide (oral) RybelsusoralDiabetes
First oral GLP-1 (for diabetes).
Approved: Sep 20, 2019
Class: GLP-1 receptor agonist
Mechanism: GLP-1 agonist · oral
Oral tablet (7 mg, 14 mg) for glycemic control in type 2 diabetes – proof that a GLP-1 peptide could be given by mouth.
Kidney considerations: No renal dose adjustment.
Safety: Class boxed warning (thyroid C-cell tumours); take fasting with limited water per label.
Source: FDA approval history
2020
Lorcaserin withdrawn BelviqoralWithdrawn
Withdrawn over a cancer signal.
Approved: Feb 13, 2020
Class: 5-HT2C agonist
Mechanism: Serotonergic / monoamine · oral
FDA requested market withdrawal after a long-term safety trial showed more cancer cases in treated patients.
Source: FDA drug safety communication
2020
Setmelanotide ImcivreeinjectableObesity approval
First drug for rare genetic obesity.
Typical weight loss: Rare genetic obesity: mean -25.6% (POMC) / -12.5% (LEPR), single-arm – a different endpoint from the drugs above
Approved: Nov 27, 2020
Class: MC4R agonist
Mechanism: MC4R agonist · injectable
Chronic weight management in obesity due to POMC, PCSK1 or LEPR deficiency confirmed by genetic testing; initially ages ≥6 (FDA approval letter Nov 25, 2020). Later expanded to Bardet-Biedl syndrome, ages ≥6, on Jun 16, 2022 (FDA news release), and to ages ≥2 in December 2024 (FDA label, rev. 12/2024). Not comparable to common polygenic obesity.
Kidney considerations: No specific renal dose adjustment established.
Safety: Skin hyperpigmentation, injection-site reactions, nausea; disturbances of sexual arousal / priapism – monitor.
Source: FDA news release
2020
Liraglutide adolescents SaxendainjectableIndication expansion
First GLP-1 obesity approval in ages 12-17.
Approved: Dec 4, 2020
Class: GLP-1 receptor agonist
Mechanism: GLP-1 agonist · injectable
Extended Saxenda to adolescents ≥12 (weight >60 kg, meeting BMI criteria).
Source: FDA news release
2021
Semaglutide WegovyinjectableObesity approval
2.4 mg weekly – a step-change in efficacy.
Typical weight loss: -14.9% vs -2.4% placebo (STEP 1, 68 wk; treatment-policy estimand)
Approved: Jun 4, 2021
Class: GLP-1 receptor agonist
Mechanism: GLP-1 agonist · injectable
First new obesity drug since 2014; ~15% mean weight loss reset expectations for the field.
Kidney considerations: No renal dose adjustment; watch dehydration / prerenal AKI with GI effects.
Safety: Boxed warning: thyroid C-cell tumours (MTC/MEN 2 contraindication). Pancreatitis, gallbladder disease, ileus; aspiration risk with anaesthesia/sedation; not in pregnancy.
Source: FDA approval letter, NDA 215256
2022
Tirzepatide MounjaroinjectableDiabetes
First dual GIP/GLP-1 agonist (for diabetes).
Approved: May 13, 2022
Class: Dual GIP/GLP-1 receptor agonist
Mechanism: GIP / GLP-1 agonist · injectable
A new mechanism combining GIP and GLP-1 activity; approved first for type 2 diabetes.
Kidney considerations: No renal dose adjustment; watch dehydration / prerenal AKI with GI effects.
Safety: Boxed warning: thyroid C-cell tumours (MTC/MEN 2 contraindication). May reduce oral-contraceptive efficacy – advise a barrier method. Pancreatitis, gallbladder disease.
2022
Qsymia adolescents QsymiaoralIndication expansion
Extended to pediatric patients ≥12.
Approved: Jun 27, 2022
Class: Sympathomimetic + antiepileptic (combination)
Mechanism: Combination · oral
Chronic weight management in adolescents ≥12 with BMI ≥95th percentile.
Source: FDA news release
2022
Semaglutide adolescents WegovyinjectableIndication expansion
Extended to ages 12+.
Approved: Dec 23, 2022
Class: GLP-1 receptor agonist
Mechanism: GLP-1 agonist · injectable
Wegovy approved for adolescents ≥12 with obesity.
Source: FDA approval history
2023
Tirzepatide ZepboundinjectableObesity approval
Dual GIP/GLP-1 approved for obesity.
Typical weight loss: -20.9% vs -3.1% placebo (SURMOUNT-1, 72 wk; treatment-regimen estimand)
Approved: Nov 8, 2023
Class: Dual GIP/GLP-1 receptor agonist
Mechanism: GIP / GLP-1 agonist · injectable
Same molecule as Mounjaro, branded for chronic weight management. Among the highest weight loss of any approved agent on a matched estimand; investigational retatrutide is higher.
Kidney considerations: No renal dose adjustment; watch dehydration / prerenal AKI with GI effects.
Safety: Boxed warning: thyroid C-cell tumours (MTC/MEN 2 contraindication). May reduce oral-contraceptive efficacy. Pancreatitis, gallbladder disease.
2024
Semaglutide – CV risk WegovyinjectableIndication expansion
First obesity drug with a cardiovascular indication.
Approved: Mar 8, 2024
Class: GLP-1 receptor agonist
Mechanism: GLP-1 agonist · injectable
Based on the SELECT trial: to reduce the risk of cardiovascular death, non-fatal MI and non-fatal stroke in adults with established cardiovascular disease and obesity or overweight.
Organ outcomes: SELECT: a 20% reduction in major cardiovascular events – the first hard-outcome indication for an obesity drug. See the Therapy Selector and CKM Explorer.
Source: FDA press announcement
2024
Generic liraglutide (diabetes) Teva authorized generic of VictozainjectableGeneric
First generic-market entry for a GLP-1.
Approved: Jun 24, 2024
Class: GLP-1 receptor agonist
Mechanism: GLP-1 agonist · injectable
Teva launched an authorized generic of Victoza (1.8 mg, diabetes) on June 24, 2024. The first FDA-approved (ANDA) generic followed from Hikma on Dec 23, 2024 (FDA release).
2024
Tirzepatide – OSA ZepboundinjectableIndication expansion
First drug for obstructive sleep apnea in obesity.
Approved: Dec 20, 2024
Class: Dual GIP/GLP-1 receptor agonist
Mechanism: GIP / GLP-1 agonist · injectable
Approved for moderate-to-severe obstructive sleep apnea in adults with obesity – an obesity drug earning a complication indication.
2025
Semaglutide – kidney (CKD) OzempicinjectableIndication expansion
First GLP-1 with a chronic-kidney-disease indication.
Approved: Jan 28, 2025
Class: GLP-1 receptor agonist
Mechanism: GLP-1 agonist · injectable
Based on the FLOW trial (type 2 diabetes with CKD): to reduce the risk of kidney-disease worsening, kidney failure (end-stage kidney disease) and death due to cardiovascular disease. The most directly nephrology-relevant approval on this timeline.
Organ outcomes: FLOW (semaglutide 1.0 mg weekly): 24% relative risk reduction in the primary composite kidney/cardiovascular outcome in type 2 diabetes with CKD. See the Therapy Selector and CKM Explorer.
Kidney considerations: Dedicated CKD indication; no renal dose adjustment. FLOW used semaglutide 1.0 mg (not the 2.4 mg obesity dose); population eGFR ~25-75 with albuminuria.
2025
Semaglutide – MASH WegovyinjectableIndication expansion
Accelerated approval for fatty-liver disease (MASH).
Approved: Aug 15, 2025
Class: GLP-1 receptor agonist
Mechanism: GLP-1 agonist · injectable
Accelerated approval for adults with non-cirrhotic metabolic dysfunction-associated steatohepatitis (MASH) with moderate-to-advanced fibrosis (F2-F3), with diet and exercise. Based on ESSENCE (63% vs 34% MASH resolution at 72 weeks). Resmetirom (Rezdiffra, 2024) was the first MASH drug.
Organ outcomes: ESSENCE: MASH resolution without worsening fibrosis in 63% vs 34%. See the Therapy Selector and CKM Explorer.
2025
Generic liraglutide (weight) Teva generic SaxendainjectableGeneric
First generic GLP-1 indicated for weight loss.
Approved: Aug 28, 2025
Class: GLP-1 receptor agonist
Mechanism: GLP-1 agonist · injectable
FDA approval and launch the same day; first generic GLP-1 with a weight-management indication (adults and ages 12-17).
2025
Semaglutide (oral, 25 mg) Wegovy tabletsoralObesity approval
First oral GLP-1 for weight management.
Typical weight loss: ~17% (OASIS 4, 64 wk)
Approved: Dec 22, 2025
Class: GLP-1 receptor agonist (oral peptide)
Mechanism: GLP-1 agonist · oral
First oral GLP-1 approved for chronic weight management, with a cardiovascular indication (reduce major adverse cardiovascular events in adults with established cardiovascular disease and overweight/obesity). A once-daily 25 mg tablet.
Kidney considerations: No renal dose adjustment; watch dehydration / prerenal AKI with GI effects.
Safety: Class boxed warning (thyroid C-cell tumours, MTC/MEN 2 contraindication). Pancreatitis, gallbladder disease; take fasting per label.
2026
Semaglutide 7.2 mg Wegovy HDinjectableNewest 2026
Higher-dose semaglutide for greater weight loss.
Typical weight loss: ~20.7% (STEP UP, 72 wk); use only after tolerating 2.4 mg for ≥4 weeks
Approved: Mar 19, 2026
Class: GLP-1 receptor agonist
Mechanism: GLP-1 agonist · injectable
A more potent 7.2 mg dose for when additional weight reduction is clinically indicated and the 2.4 mg dose has been tolerated for at least 4 weeks. Approved under the National Priority Voucher program.
Kidney considerations: No renal dose adjustment; watch dehydration / prerenal AKI with GI effects.
Safety: Class boxed warning (thyroid C-cell tumours). Altered skin sensation (paraesthesia/hyperesthesia) reported in ~22% at the higher dose vs ~6% at 2.4 mg.
2026
Setmelanotide – hypothalamic obesity ImcivreeinjectableIndication expansion
First drug for acquired hypothalamic obesity.
Typical weight loss: -18.4% placebo-adjusted BMI (TRANSCEND, 52 wk; ages ≥4)
Approved: Mar 19, 2026
Class: MC4R agonist
Mechanism: MC4R agonist · injectable
Approved to reduce and maintain body-weight reduction in adults and children ≥4 years with acquired hypothalamic obesity (e.g., after craniopharyngioma/hypothalamic injury). Based on TRANSCEND (-15.8% vs +2.6% placebo).
Kidney considerations: No specific renal dose adjustment established.
Safety: Skin hyperpigmentation, injection-site reactions, nausea; sexual-arousal effects – monitor.
2026
Orforglipron FoundayooralNewest 2026
First oral small-molecule (non-peptide) GLP-1 for obesity.
Typical weight loss: -11.2% vs -2.1% placebo (ATTAIN-1, 72 wk; treatment-regimen estimand)
Approved: Apr 1, 2026
Class: Oral small-molecule GLP-1 receptor agonist
Mechanism: GLP-1 agonist · oral
A once-daily oral tablet for adults with obesity, or overweight with ≥1 weight-related condition. Unlike oral semaglutide (a peptide), orforglipron is a small molecule with no food/water restrictions. Fastest new-molecular-entity approval since 2002, under the National Priority Voucher program.
Kidney considerations: No renal dose adjustment expected (small molecule); watch GI-related volume depletion.
Safety: Boxed warning: thyroid C-cell tumours (MTC/MEN 2 contraindication), retained for the GLP-1 class though, as a small molecule, orforglipron is not active in rodents. GI effects (nausea, vomiting, diarrhoea).
Obesity approval Diabetes Indication expansion Generic Withdrawn Newest 2026
Beyond weight — proven outcomes for selected agents (not a class effect). Semaglutide 2.4 mg reduced major adverse cardiovascular events in adults with established cardiovascular disease and overweight or obesity without diabetes (SELECT, indication 2024). Semaglutide 1.0 mg reduced the primary composite kidney outcome in adults with type 2 diabetes and chronic kidney disease (FLOW, indication 2025). These results are agent-, dose-, population- and endpoint-specific and should not be generalised to all GLP-1 or GIP/GLP-1 agonists. How SGLT2 inhibitors, GLP-1 agonists and finerenone are layered to protect the heart and kidney is the focus of our Organ-Protective Therapy Selector and CKM Explorer.
On the horizon — investigational, not FDA-approved as of July 2026: retatrutide, a triple GIP/GLP-1/glucagon agonist, reported positive Phase 3 topline results (TRIUMPH-1, May 2026; about 28% mean weight loss, company-reported and pending peer-reviewed publication), with further trials ongoing. CagriSema, a fixed-dose combination of the amylin analogue cagrilintide and semaglutide, was submitted to the FDA in December 2025 and remains under review.
Scope: US FDA approvals for weight management (and closely related diabetes/kidney/cardiovascular indications of the same molecules). Historical amphetamine derivatives (e.g., mazindol) and lipodystrophy therapeutics (e.g., metreleptin) are outside scope. Withdrawn products are clearly identified, and a separate horizon section lists selected investigational agents. Bariatric and endoscopic procedures are not shown.
Primary sources: US FDA – Drugs@FDA (accessdata.fda.gov), FDA press announcements (fda.gov/news-events), FDA drug-safety communications, and the Federal Register for withdrawals; pivotal-trial publications (XENDOS, EQUIP/CONQUER, COR-I, SCALE, STEP 1, SURMOUNT-1, FLOW, ESSENCE, OASIS 4, STEP UP, ATTAIN-1, TRANSCEND) for efficacy. Weight-loss figures are cross-trial, not head-to-head, and the estimand is named where available. A few pre-2000 withdrawn agents cite the FDA post-market safety archive.
Educational use only. This timeline documents the regulatory history of obesity pharmacotherapy, for health professionals, trainees, and students. It is not medical advice, does not establish a doctor–patient relationship, and does not replace clinical judgement or the full prescribing information. Always consult a qualified clinician for care decisions. See the full medical disclaimer.