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    ● Developing story

    GLP-1 and metabolic medicine tracker

    Since 2023 GLP-1 medicine has moved from weekly injections for weight loss to approvals for heart, kidney, liver and sleep-apnea indications, two FDA-approved pills, and new US coverage.[1][2][3][4] Peer-reviewed phase 3 retatrutide results appeared in September 2026. The next milestones are an FDA decision on CagriSema and Lilly's planned retatrutide filing.[5][6][7]

    Editor reviewedStrict sourcingUpdated GLP-1 and metabolic medicineHealth and medicineLife sciences

    What we know

    • Two GLP-1 pills are FDA-approved for weight management: the Wegovy pill (Dec 2025) and Foundayo (Apr 2026).[3]
    • Semaglutide reduced major cardiovascular events by about 20% in people with obesity and heart disease but no diabetes (SELECT).[33]
    • Tirzepatide produced more weight loss than semaglutide head-to-head (20.2% vs 13.7% at 72 weeks).[12]
    • Lilly plans to file retatrutide with the FDA in Q1 2027.[7]
    • In the peer-reviewed TRIUMPH-1 paper, retatrutide 12 mg produced -25.0% weight change at 80 weeks versus -3.9% on placebo (intention-to-treat); Lilly's 28.3% topline used an efficacy estimand.[5]
    • Tirzepatide (Mounjaro) gained a US cardiovascular risk-reduction indication in type 2 diabetes in August 2026.[20]
    • Oral orforglipron was non-inferior to insulin glargine for major cardiovascular events in ACHIEVE-4.[21]
    • Medicare's GLP-1 Bridge offers certain GLP-1s for $50 a month from 1 July 2026 to 31 December 2027.[4]
    • Most weight lost on GLP-1s returns after stopping treatment.[34]

    What we don't know yet

    • Whether the FDA will approve CagriSema, and on what label, by its expected late-2026 decision.
    • When the FDA will decide on orforglipron for type 2 diabetes, filed in the second quarter of 2026.
    • How regulators will weigh retatrutide's dysesthesia and hypotension signals.
    • What will replace Medicare's GLP-1 Bridge when it ends in December 2027.
    • Whether the FDA will finalise its proposal to bar outsourcing facilities from compounding semaglutide, tirzepatide and liraglutide from bulk.
    • How safe and effective decades of continuous GLP-1 treatment will be.
    • How fast generic semaglutide will spread beyond the markets where exclusivity has already lapsed, and what it will do to prices.
    Story status

    Story status

    State
    developing
    Started
    2021-02-10
    Timeline entries
    30
    Last entry

    Timeline data (JSON)

    This tracker follows the frontier of GLP-1 and metabolic medicine. Its start date marks the publication of the STEP 1 trial in February 2021, which showed a mean 14.9% weight loss with weekly semaglutide.[8] Entries are confirmed from primary sources unless marked “reported”. Company topline results that have not yet been peer-reviewed, such as Lilly’s May 2026 TRIUMPH-1 announcement, are marked reported.[9]

    Where things stand (October 2026)

    semaglutide and tirzepatide dominate the market. Semaglutide has outcome-based approvals for heart, kidney and liver. Tirzepatide has shown more weight loss head-to-head and has a sleep-apnea approval.[1][10][11][12][13] Two pills are now approved, and US weekly prescriptions of the Wegovy pill passed 265,000 by July 2026.[14][3] In the US, a White House agreement, the Medicare Bridge and Medicare negotiation have cut prices for government programmes.[15][4][16]

    What changed since August 2026

    Retatrutide in print. The full TRIUMPH-1 results appeared in NEJM on 29 September 2026. Under the primary intention-to-treat analysis, mean weight change at 80 weeks was -25.0% at 12 mg versus -3.9% on placebo. Retatrutide also reduced knee-osteoarthritis pain and sleep-apnea events in subgroups.[5][17] TRIUMPH-2, in people with type 2 diabetes, reported -18.8% versus -5.1%, with more hypotension and dysesthesia than placebo.[18][19]

    Why the numbers differ. Lilly’s May figure of 28.3% used an efficacy estimand, which estimates the effect in people who stay on the drug. The NEJM paper leads with the treatment-regimen estimand, which counts everyone randomised.[5] Comparing a company topline with another drug’s published intention-to-treat result can therefore overstate the gap.

    Hearts and pills. Lilly announced on 28 August that the FDA had approved Mounjaro to lower cardiovascular risk in high-risk type 2 diabetes, based on SURPASS-CVOT.[20] On 30 September, ACHIEVE-4 showed that the orforglipron pill was non-inferior to insulin glargine for major cardiovascular events (hazard ratio 0.84).[21]

    More competition. Novo reported that low-dose cagrisema beat tirzepatide 5 mg in REIMAGINE 5 (topline).[22] Boehringer Ingelheim’s survodutide, a glucagon/GLP-1 dual agonist, produced -9.8% versus -3.9% at 76 weeks in obesity with type 2 diabetes.[23] Lilly reported phase 2b data for an amylin-plus-tirzepatide combination.[24]

    What to watch next

    • CagriSema decision. Novo expects an FDA decision by late 2026.[6]
    • Retatrutide filing. Lilly plans a Biologics License Application in the first quarter of 2027.[7]
    • Maintenance strategies. Whether switching from injections to a pill holds weight off beyond a year; ATTAIN-MAINTAIN lasted 52 weeks and had no arm that stayed on injections.[25][26]
    • Orforglipron for diabetes. Lilly filed it for type 2 diabetes in the second quarter of 2026, and ACHIEVE-4 now supplies cardiovascular safety data.[27][21]
    • Compounding. The FDA’s final decision on excluding semaglutide, tirzepatide and liraglutide from the 503B bulks list.[28]
    • Coverage after 2027. The Medicare Bridge ends on 31 December 2027, the same year negotiated semaglutide prices take effect.[4][16]
    • Generics and global access. Further loss of semaglutide exclusivity outside the US, and progress against WHO’s projection that fewer than 10% of those who could benefit will be reached by 2030.[29][30]
    • New entrants. Monthly and amylin-based candidates from companies including Pfizer (via Metsera) and Amgen (MariTide).[31][32]

    Timeline

    27 confirmed3 reported

    1. confirmed

      Survodutide SYNCHRONIZE-2 phase 3 results in obesity with type 2 diabetes published in NEJM[23]

    2. confirmed

      ACHIEVE-4 shows orforglipron is non-inferior to insulin glargine on heart events[21][50]

    3. reported

      Lilly reports EloraTZP (eloralintide plus tirzepatide) phase 2b results (company data)[24]

    4. confirmed

      Full TRIUMPH-1 (NEJM) and TRIUMPH-2 (Lancet) retatrutide results published[5][17][18]

    5. confirmed

      FDA approves Lilly's once-weekly insulin Onswik[49]

    6. reported

      Novo reports CagriSema beat tirzepatide 5 mg in REIMAGINE 5 (company topline)[22]

    7. confirmed

      FDA approves Mounjaro to lower cardiovascular risk in type 2 diabetes (Lilly announcement)[20][48]

    8. confirmed

      Lilly sues black-market retatrutide sellers, stressing no approved product exists[47]

    9. confirmed

      Lilly says retatrutide data package is complete, plans Q1 2027 filing[7]

    10. confirmed

      Novo Nordisk raises 2026 outlook on stronger GLP-1 demand[45][14]

    11. confirmed

      Medicare GLP-1 Bridge begins offering obesity drugs for $50 a month[4][44]

    12. confirmed

      CagriSema REIMAGINE 3 results in insulin-treated type 2 diabetes published in The Lancet[46]

    13. reported

      Retatrutide shows 28.3% average weight loss in phase 3 TRIUMPH-1 (company topline)[9]

    14. confirmed

      ATTAIN-MAINTAIN shows orforglipron pill preserves most weight lost on injections[25]

    15. confirmed

      FDA proposes ending bulk compounding of semaglutide and tirzepatide by outsourcing facilities[28]

    16. confirmed

      FDA approves Lilly's orforglipron (Foundayo) pill[3]

    17. confirmed

      CagriSema misses non-inferiority against tirzepatide in REDEFINE 4[43]

    18. confirmed

      FDA approves the Wegovy pill, first oral GLP-1 for weight management[2]

    19. confirmed

      WHO issues first guideline on GLP-1 medicines for obesity[42]

    20. confirmed

      Medicare negotiated price of $274 set for semaglutide, effective 2027[16]

    21. confirmed

      Semaglutide fails to slow Alzheimer's disease in evoke trials[41]

    22. confirmed

      White House pricing agreement with Lilly and Novo sets $245 Medicare price[15]

    23. confirmed

      Wegovy gets accelerated approval for MASH with fibrosis[11]

    24. confirmed

      FDA declares US semaglutide shortage resolved[40]

    25. confirmed

      Ozempic label expanded to kidney disease in type 2 diabetes, based on FLOW[10][39]

    26. confirmed

      Lancet Commission defines "clinical" and "preclinical" obesity[37][38]

    27. confirmed

      Zepbound becomes first drug approved for obstructive sleep apnea[13]

    28. confirmed

      FDA declares US tirzepatide shortage resolved[36]

    29. confirmed

      Wegovy approved to cut cardiovascular risk, based on SELECT[1][33]

    30. confirmed

      FDA approves Zepbound (tirzepatide) for chronic weight management[35]

    Sources

    Each numbered claim is a statement we checked against the sources listed with it. Status shows how well established it is.

    1. [1]

      On 8 March 2024 the FDA approved Wegovy to reduce the risk of cardiovascular death, heart attack and stroke in adults with cardiovascular disease and obesity or overweight, the first weight-loss medicine with such an indication. confirmedas of 2024-03-08

    2. [2]

      On 22 December 2025 the FDA approved the Wegovy pill (once-daily oral semaglutide 25 mg), the first oral GLP-1 receptor agonist approved for weight management, including to reduce cardiovascular risk. confirmedas of 2025-12-22

    3. [3]

      On 1 April 2026 the FDA approved Lilly's orforglipron, branded Foundayo, for adults with obesity or overweight with weight-related conditions, under the National Priority Voucher pilot about 50 days after filing. confirmedas of 2026-04-01

    4. [4]

      CMS's Medicare GLP-1 Bridge, a time-limited demonstration, gives eligible Part D enrollees certain GLP-1 medicines for $50 a month from 1 July 2026 through 31 December 2027. confirmedas of 2026-05-06

    5. [5]

      The peer-reviewed TRIUMPH-1 report (NEJM, 29 September 2026) gave mean weight changes at 80 weeks of -17.6%, -23.7% and -25.0% with retatrutide 4, 9 and 12 mg versus -3.9% with placebo under the treatment-regimen (intention-to-treat) estimand; Lilly's May topline figures of 19.0%, 25.9% and 28.3% used the efficacy estimand. confirmedas of 2026-09-29

    6. [6]

      Novo Nordisk submitted CagriSema to the US FDA in December 2025 based on REDEFINE 1 and 2, with a decision anticipated by late 2026. confirmedas of 2026-09-21

    7. [7]

      As of August 2026, Lilly said three additional phase 3 retatrutide obesity trials were positive, that the data package was complete for obesity, obstructive sleep apnea and knee osteoarthritis pain, and that it plans to submit a Biologics License Application to the FDA in the first quarter of 2027. confirmedas of 2026-08-05

    8. [8]

      In the STEP 1 trial, weekly semaglutide 2.4 mg plus lifestyle intervention produced a mean 14.9% weight loss at 68 weeks versus 2.4% with placebo. confirmedas of 2021-02-10

    9. [9]

      Lilly reported on 21 May 2026 that in the phase 3 TRIUMPH-1 trial of 2,339 adults with obesity or overweight without diabetes, retatrutide 12 mg produced an average 28.3% weight loss at 80 weeks. confirmedas of 2026-05-21

    10. [10]

      On 28 January 2025 the FDA expanded Ozempic's label to reduce kidney and cardiovascular risks in adults with type 2 diabetes and chronic kidney disease. confirmedas of 2025-01-28

    11. [11]

      In August 2025 the FDA granted Wegovy accelerated approval for noncirrhotic MASH with moderate to advanced (F2 to F3) liver fibrosis. confirmedas of 2025-08-15

    12. [12]

      In the open-label SURMOUNT-5 trial, people with obesity but without diabetes lost a mean 20.2% of body weight on tirzepatide versus 13.7% on semaglutide at 72 weeks. confirmedas of 2025-05-11

    13. [13]

      On 20 December 2024 the FDA approved Zepbound for moderate to severe obstructive sleep apnea in adults with obesity, the first drug treatment for the condition. confirmedas of 2024-12-20

    14. [14]

      By mid-July 2026, US weekly prescriptions for the Wegovy pill exceeded 265,000, with more than 5 million prescriptions since launch. confirmedas of 2026-08-04

    15. [15]

      Under a 6 November 2025 agreement announced by the White House with Eli Lilly and Novo Nordisk, Medicare prices for Ozempic, Wegovy, Mounjaro and Zepbound were set at $245 a month with a $50 monthly copay for beneficiaries, and Ozempic and Wegovy at $350 through the TrumpRx website. confirmedas of 2025-11-06

    16. [16]

      Under the Medicare Drug Price Negotiation Program, CMS set a negotiated 30-day price of $274 for Ozempic, Rybelsus and Wegovy, against a 2024 list price of $959, effective 1 January 2027. confirmedas of 2025-11-25

    17. [17]

      In TRIUMPH-1, retatrutide also reduced knee osteoarthritis pain in 574 participants with the condition and reduced apnea-hypopnea events in 243 participants with obstructive sleep apnea, compared with placebo. confirmedas of 2026-09-29

    18. [18]

      In the phase 3 TRIUMPH-2 trial of 1,152 adults with obesity and type 2 diabetes (The Lancet, September 2026), mean weight change at 80 weeks was -11.9%, -16.8% and -18.8% with retatrutide 4, 9 and 12 mg versus -5.1% with placebo; gastrointestinal events were the most common adverse events. confirmedas of 2026-09-29

    19. [19]

      In TRIUMPH-2, hypotension and dysesthesia (abnormal skin sensations) were more frequent with retatrutide than placebo, and permanent discontinuation for adverse events or death was 12% at 9 mg and 8% at 12 mg versus 5% with placebo. confirmedas of 2026-09-29

    20. [20]

      Lilly announced on 28 August 2026 that the FDA approved Mounjaro (tirzepatide) to lower the risk of major adverse cardiovascular events in adults with type 2 diabetes at high risk of them, based on SURPASS-CVOT. confirmedas of 2026-08-28

    21. [21]

      In the open-label ACHIEVE-4 trial of 2,749 adults with type 2 diabetes at increased cardiovascular risk (The Lancet, 30 September 2026), oral orforglipron was non-inferior to insulin glargine for major adverse cardiovascular events (4.2% vs 5.0%; hazard ratio 0.84, 95% CI 0.59 to 1.20) over a median 2 years. confirmedas of 2026-09-30

    22. [22]

      Novo Nordisk reported topline results on 21 September 2026 in which CagriSema 1.0 mg/1.0 mg produced 12.4% weight loss versus 9.1% with tirzepatide 5 mg in type 2 diabetes (REIMAGINE 5), and 21.0% versus 2.0% with placebo in obesity (REDEFINE 9). reportedas of 2026-09-21

    23. [23]

      In the phase 3 SYNCHRONIZE-2 trial of 752 adults with obesity and type 2 diabetes, Boehringer Ingelheim's glucagon/GLP-1 dual agonist survodutide produced mean weight changes of -8.2% and -9.8% at 76 weeks versus -3.9% with placebo. confirmedas of 2026-10-01

    24. [24]

      Lilly reported on 30 September 2026 that in a 48-week phase 2b trial in 367 adults with obesity and type 2 diabetes, its eloralintide (amylin agonist) plus tirzepatide combination produced up to 23.3% weight loss versus 14.8% with tirzepatide 15 mg alone, and that phase 3 trials would start in Q4 2026. reportedas of 2026-09-30

    25. [25]

      In the phase 3b ATTAIN-MAINTAIN trial, people who switched from injectable tirzepatide or semaglutide to daily orforglipron kept an estimated 74.7% and 79.3% of their prior weight loss at 52 weeks, versus 49.2% and 37.6% with placebo. confirmedas of 2026-05-13

    26. [26]

      The ATTAIN-MAINTAIN authors noted that the trial had no comparator arm continuing injectable obesity medicines and lasted only one year. confirmedas of 2026-05-13

    27. [27]

      In the second quarter of 2026 Lilly submitted orforglipron to the FDA for type 2 diabetes. confirmedas of 2026-08-05

    28. [28]

      On 30 April 2026 the FDA proposed excluding semaglutide, tirzepatide and liraglutide from the 503B bulks list, which would bar outsourcing facilities from compounding them from bulk ingredients; comments were accepted until 29 June 2026. confirmedas of 2026-04-30

    29. [29]

      Novo Nordisk reported that loss of exclusivity for semaglutide in Canada and certain other international markets, together with the US most-favoured-nation agreement, lowered its realised prices in 2026. confirmedas of 2026-08-04

    30. [30]

      WHO projects that even with expanded production, GLP-1 therapies will reach fewer than 10% of those who could benefit by 2030. confirmedas of 2025-12-01

    31. [31]

      Pfizer completed its acquisition of obesity-drug developer Metsera on 13 November 2025 at about $7.0 billion enterprise value plus contingent payments tied to its monthly injectable GLP-1 candidate MET-097i and amylin analogue MET-233i. confirmedas of 2025-11-13

    32. [32]

      Amgen's maridebart cafraglutide (MariTide), a monthly peptide-antibody conjugate that activates the GLP-1 receptor and blocks the GIP receptor, produced mean weight loss of 12.3% to 16.2% at 52 weeks versus 2.5% with placebo in a phase 2 obesity trial. confirmedas of 2026-10-10

    33. [33]

      In the SELECT trial of 17,604 adults aged 45 or older with cardiovascular disease and overweight or obesity but no diabetes, semaglutide 2.4 mg reduced cardiovascular death, heart attack or stroke to 6.5% versus 8.0% on placebo (hazard ratio 0.80). confirmedas of 2023-11-11

    34. [34]

      A 2026 BMJ meta-analysis of 37 studies found average weight regain of 0.4 kg per month after stopping weight-management medicines, with cardiometabolic markers projected to return to baseline within 1.4 years, faster than after behavioural programmes. confirmedas of 2026-01-07

    35. [35]

      On 8 November 2023 the FDA approved Zepbound (tirzepatide) for chronic weight management in adults with obesity, or overweight with at least one weight-related condition. confirmedas of 2023-11-08

    36. [36]

      The FDA determined on 19 December 2024 that the US shortage of tirzepatide injection had been resolved. confirmedas of 2024-12-19

    37. [37]

      The Lancet Diabetes & Endocrinology Commission defines clinical obesity as a chronic, systemic illness in which excess or abnormal body fat alters the function of tissues, organs or the person. confirmedas of 2025-01-14

    38. [38]

      The Commission, published on 14 January 2025, involved 58 experts and was endorsed by 76 organisations. confirmedas of 2025-01-14

    39. [39]

      In the FLOW trial of 3,533 people with type 2 diabetes and chronic kidney disease, semaglutide lowered the risk of major kidney events or kidney- or cardiovascular-related death by 24% (hazard ratio 0.76); the trial stopped early at a prespecified interim analysis after a median 3.4 years of follow-up. confirmedas of 2024-05-24

    40. [40]

      The FDA determined on 21 February 2025 that the US shortage of semaglutide injection products was resolved, ending temporary leeway for compounders to make copies after set grace periods. confirmedas of 2025-02-21

    41. [41]

      On 24 November 2025 Novo Nordisk reported that the evoke and evoke+ trials in 3,808 adults with early Alzheimer's disease did not show that semaglutide slowed disease progression, although Alzheimer's biomarkers improved. confirmedas of 2025-11-24

    42. [42]

      On 1 December 2025 WHO issued its first guideline on GLP-1 medicines for obesity, with conditional recommendations that adults may use them for long-term treatment alongside behavioural interventions. confirmedas of 2025-12-01

    43. [43]

      On 23 February 2026 Novo Nordisk reported that CagriSema failed to show non-inferiority to tirzepatide 15 mg in the open-label REDEFINE 4 trial, with weight loss of 20.2% versus 23.6% at 84 weeks under the treatment-regimen estimand. confirmedas of 2026-02-23

    44. [44]

      Novo Nordisk reported that the Bridge programme began on 1 July 2026 and covers a majority of Medicare beneficiaries, and Lilly reported Foundayo and Zepbound coverage under it. confirmedas of 2026-08-05

    45. [45]

      On 4 August 2026 Novo Nordisk raised its 2026 outlook to adjusted sales growth of 0% to -6% at constant exchange rates, from -4% to -12%, citing higher expected GLP-1 sales. confirmedas of 2026-08-04

    46. [46]

      In REIMAGINE 3, CagriSema added to basal insulin in type 2 diabetes lowered HbA1c by 2.33 and 2.10 percentage points at the 2.4 mg and 1.0 mg doses versus 0.66 with placebo at 40 weeks, with 10-12% weight reduction and no severe hypoglycaemia. confirmedas of 2026-06-07

    47. [47]

      In August 2026 Lilly said no retatrutide medicine had been approved anywhere, filed six lawsuits against US sellers of black-market retatrutide and said it had reported more than 14,000 websites, ads and listings marketing it illegally. confirmedas of 2026-08-12

    48. [48]

      In SURPASS-CVOT, tirzepatide was non-inferior but not shown superior to dulaglutide, a GLP-1 drug previously shown to reduce cardiovascular events, for cardiovascular death, heart attack or stroke in 13,165 people with type 2 diabetes and heart disease (hazard ratio 0.92), using a non-inferiority margin of 1.05. confirmedas of 2025-12-01

    49. [49]

      Lilly announced on 24 September 2026 FDA approval of Onswik (insulin efsitora alfa), a once-weekly basal insulin for adults with type 2 diabetes, following approvals in the EU, Mexico and Japan. confirmedas of 2026-09-24

    50. [50]

      In ACHIEVE-4, gastrointestinal adverse events occurred in 62.1% of orforglipron patients versus 14.2% on insulin glargine, while clinically significant or severe hypoglycaemia was less frequent (6.8% vs 19.2%). confirmedas of 2026-09-30

    Revision history (2)
    1. Page created.
    2. Refresh: extended the timeline from August to October 2026 (Mounjaro cardiovascular approval, retatrutide NEJM and Lancet papers, ACHIEVE-4, REIMAGINE 5, Onswik, survodutide) and explained the estimand difference.

    Created Oct 10, 2026. Last reviewed by an editor on Oct 10, 2026. Next scheduled review: Dec 10, 2026.

    Cite this page

    "GLP-1 and metabolic medicine tracker." ContentLora, updated Oct 10, 2026. https://contentlora.com/events/metabolic-medicine-tracker

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