K4 Elite
K4 Elite
Tirzepatide is a once-weekly GIP and GLP-1 receptor agonist that is FDA-approved as Mounjaro (type 2 diabetes) and Zepbound (chronic weight management; obstructive sleep apnoea). It has been studied in large Phase 3 programmes: SURPASS in type 2 diabetes (including the head-to-head SURPASS-2 trial versus semaglutide 1 mg) and SURMOUNT in obesity/overweight (SURMOUNT-1 versus placebo; SURMOUNT-5 versus semaglutide 2.4 mg). Adverse-event, interaction and contraindication data below are taken from the trial abstracts and the current Zepbound prescribing information.
Each row records what a published study did: who it enrolled, the regimen it administered to those subjects, and what it reported. These are historical study descriptions, not protocols to follow.
| Study | Population | Regimen as reported | Primary findings |
|---|---|---|---|
| SURMOUNT-1 — Jastreboff et al., NEJM 2022 (Phase 3) Registry: NCT04184622
|
Adults with BMI >=30, or >=27 with at least one weight-related complication, excluding diabetes (n=2,539); mean baseline weight 104.8 kg, mean BMI 38.0 | Participants were assigned 1:1:1:1 to once-weekly subcutaneous tirzepatide 5 mg, 10 mg or 15 mg, or placebo, for 72 weeks including a 20-week dose-escalation period. | Mean percentage change in weight at week 72 was -15.0% (5 mg), -19.5% (10 mg) and -20.9% (15 mg) versus -3.1% with placebo; adverse events led to discontinuation in 4.3%, 7.1%, 6.2% and 2.6% respectively. |
| SURMOUNT-5 — Aronne et al., NEJM 2025 (Phase 3b, open-label, vs semaglutide) Registry: NCT05822830
|
Adults with obesity but without type 2 diabetes (n=751 randomised) | Participants were randomly assigned 1:1 to the maximum tolerated dose of tirzepatide (10 mg or 15 mg) or of semaglutide (1.7 mg or 2.4 mg) subcutaneously once weekly for 72 weeks. | Least-squares mean percent change in weight at week 72 was -20.2% with tirzepatide versus -13.7% with semaglutide; the most common adverse events in both groups were gastrointestinal, mostly mild to moderate and occurring primarily during dose escalation. |
| SURPASS-2 — Frías et al., NEJM 2021 (Phase 3, open-label, vs semaglutide 1 mg) Registry: NCT03987919
|
Patients with type 2 diabetes (n=1,879); mean baseline HbA1c 8.28%, mean weight 93.7 kg | Patients were randomly assigned 1:1:1:1 to tirzepatide 5 mg, 10 mg or 15 mg, or semaglutide 1 mg, once weekly for 40 weeks. | Estimated mean change in HbA1c from baseline to 40 weeks was -2.01, -2.24 and -2.30 percentage points with tirzepatide 5, 10 and 15 mg versus -1.86 with semaglutide; tirzepatide was noninferior and superior at all doses. |
Effects recorded in the cited reports. Frequencies are those the source reported, in the population that source studied.
| Effect | Frequency / context | Source |
|---|---|---|
| Nausea | 25% (5 mg), 29% (10 mg), 28% (15 mg) vs 8% placebo in the pooled placebo-controlled weight-reduction trials (Zepbound label, Table 1). | ZEPBOUND (tirzepatide) injection — Prescribing Information (DailyMed) ↗ |
| Diarrhoea | 19% (5 mg), 21% (10 mg), 23% (15 mg) vs 8% placebo (Zepbound label, Table 1). | ZEPBOUND (tirzepatide) injection — Prescribing Information (DailyMed) ↗ |
| Vomiting | 8% (5 mg), 11% (10 mg), 13% (15 mg) vs 2% placebo (Zepbound label, Table 1). | ZEPBOUND (tirzepatide) injection — Prescribing Information (DailyMed) ↗ |
| Constipation | 17% (5 mg), 14% (10 mg), 11% (15 mg) vs 5% placebo (Zepbound label, Table 1). | ZEPBOUND (tirzepatide) injection — Prescribing Information (DailyMed) ↗ |
| Abdominal pain / dyspepsia | Abdominal pain 9-10% vs 5% placebo; dyspepsia 9-10% vs 4% placebo (Zepbound label, Table 1). | ZEPBOUND (tirzepatide) injection — Prescribing Information (DailyMed) ↗ |
| Injection-site reactions | 6-8% vs 2% placebo; more frequent in patients with anti-tirzepatide antibodies (11.3% vs 1%) (Zepbound label). | ZEPBOUND (tirzepatide) injection — Prescribing Information (DailyMed) ↗ |
| Fatigue | 5-7% vs 3% placebo (Zepbound label, Table 1). | ZEPBOUND (tirzepatide) injection — Prescribing Information (DailyMed) ↗ |
| Hypersensitivity reactions | 5% vs 3% placebo in Table 1; immediate hypersensitivity 2.1% vs 0.4%; serious reactions including anaphylaxis and angioedema reported (Zepbound label). | ZEPBOUND (tirzepatide) injection — Prescribing Information (DailyMed) ↗ |
| Hair loss | 4-5% vs 1% placebo; 7.1% of female vs 0.5% of male tirzepatide-treated patients (Zepbound label). | ZEPBOUND (tirzepatide) injection — Prescribing Information (DailyMed) ↗ |
| Hypotension | 1.6% vs 0.1% placebo in the pooled trials; 2.2% in those on concomitant antihypertensives (Zepbound label). | ZEPBOUND (tirzepatide) injection — Prescribing Information (DailyMed) ↗ |
| Acute gallbladder disease | Cholelithiasis 1.1% vs 1% placebo; cholecystitis 0.7% vs 0.2%; cholecystectomy 0.2% vs 0% (Zepbound label). | ZEPBOUND (tirzepatide) injection — Prescribing Information (DailyMed) ↗ |
| Acute pancreatitis | 0.2% adjudication-confirmed in both tirzepatide and placebo groups of the pooled weight-reduction trials (0.14 vs 0.15 per 100 patient-years); 0.23 vs 0.11 per 100 patient-years in type 2 diabetes trials (Zepbound label). | ZEPBOUND (tirzepatide) injection — Prescribing Information (DailyMed) ↗ |
| Hypoglycaemia (plasma glucose <54 mg/dL) | 4.2% vs 1.3% placebo in patients with type 2 diabetes (Study 2); 0.3% vs 0% in those without diabetes (Study 1) (Zepbound label). In SURPASS-2, 0.6%/0.2%/1.7% with tirzepatide 5/10/15 mg vs 0.4% with semaglutide. | Tirzepatide versus Semaglutide Once Weekly in Patients with Type 2 Diabetes ↗ |
| Heart-rate increase | Mean increase of 1 to 3 beats per minute versus no increase with placebo (Zepbound label). | ZEPBOUND (tirzepatide) injection — Prescribing Information (DailyMed) ↗ |
| Dysesthesia | 0.2% (5 mg), 0.2% (10 mg), 0.4% (15 mg) vs 0.1% placebo (Zepbound label). | ZEPBOUND (tirzepatide) injection — Prescribing Information (DailyMed) ↗ |
| Discontinuation due to adverse reactions | 4.8% (5 mg), 6.3% (10 mg), 6.7% (15 mg) vs 3.4% placebo across the pooled trials, mostly gastrointestinal and in the first months (Zepbound label). | ZEPBOUND (tirzepatide) injection — Prescribing Information (DailyMed) ↗ |
Interactions documented in trial reports, prescribing information or pharmacology references.
| Agent | Type | Note | Source |
|---|---|---|---|
| Insulin / insulin secretagogues (e.g., sulfonylureas) | pharmacodynamic | The prescribing information states that tirzepatide lowers blood glucose and that concomitant use may increase the risk of hypoglycaemia, including severe hypoglycaemia; dose reduction of insulin or secretagogue may be necessary. | ZEPBOUND (tirzepatide) injection — Prescribing Information, section 7.1 (DailyMed) ↗ |
| Oral medications generally (including narrow-therapeutic-index drugs such as warfarin) | pharmacokinetic (delayed gastric emptying) | Tirzepatide delays gastric emptying and has the potential to impact absorption of concomitantly administered oral medications; the label advises monitoring of drugs dependent on threshold concentrations or with a narrow therapeutic index. Acetaminophen Cmax was reduced by 55% after a first 5 mg dose, with no meaningful effect after repeated dosing. | ZEPBOUND (tirzepatide) injection — Prescribing Information, sections 7.2 and 12.3 (DailyMed) ↗ |
| Oral hormonal contraceptives | pharmacokinetic (reduced absorption) | With a single 5 mg tirzepatide dose, mean Cmax of ethinyl estradiol, norgestimate and norelgestromin was reduced by 59%, 66% and 55% and AUC by 20-23%; the label advises switching to a non-oral method or adding a barrier method for 4 weeks after initiation and after each dose escalation. | ZEPBOUND (tirzepatide) injection — Prescribing Information, sections 7.2 and 12.3 (DailyMed) ↗ |
| Antihypertensive therapy | pharmacodynamic | Hypotension was more frequent in tirzepatide-treated patients on concomitant antihypertensive therapy (2.2%) than in those not on antihypertensives (1.2%). | ZEPBOUND (tirzepatide) injection — Prescribing Information, section 6.1 (DailyMed) ↗ |
Exclusions and label contraindications recorded in the cited sources.