检索问题
替尔泊肽 有电解质紊乱的不良反应么
是的，替尔泊肽（Tirzepatide）确实会引起电解质紊乱的不良反应，并且在某些情况下这种紊乱可能是极其严重甚至危及生命的。
不过，我们需要明白，这款药物通常不是直接像“搞破坏”一样去消耗你体内的电解质。它引起电解质紊乱的方式，更像推倒了一块多米诺骨牌：它最常见的副作用是严重的肠胃不适（比如频繁的呕吐和腹泻），这些症状会导致身体大量流失水分和盐分，从而间接引发严重的电解质失衡（如缺钾、缺镁）。此外，它还可能通过影响体内激素的调节，或者与其他药物（如降压药）发生冲突，导致血液中的钠离子过低或钙离子过高。
为了让您彻底明白这是怎么回事，我们需要先把一些基础概念用大白话捋清楚，然后再看看真实发生过的医疗案例。
第一步：认识替尔泊肽与“电解质”
替尔泊肽是一种近年来非常受关注的药物，主要用于治疗2型糖尿病和肥胖症（也就是帮人减肥）。你可以把它想象成身体里两种天然肠道激素（GIP和GLP-1）的“模仿者”。当我们吃饭后，肠道会分泌这些激素，告诉大脑“我吃饱了”，同时告诉胰腺“赶紧分泌胰岛素来降血糖”。替尔泊肽就是通过模仿这些信号，让人不觉得饿，从而达到控制血糖和大幅度减轻体重的效果。
那么，什么是“电解质”呢？简单来说，电解质就是我们血液和体液里带电的盐分和矿物质，比如钠、钾、钙、镁。你可以把人体想象成一台极其复杂的电动机器，而电解质就是机器里的“导电液”。如果没有了它们，或者它们的比例乱了，心脏的跳动就会失去节律，肌肉会抽筋，大脑的信号也会短路。
危机一：“连拉带吐”引发的电解质大崩盘
替尔泊肽最出名、也最常见的副作用就是胃肠道反应。在大型的临床试验中，使用该药物的患者里，有17%到22%的人会感到恶心，13%到16%的人会拉肚子，还有6%到10%的人会呕吐。这些症状大多发生在刚开始用药或者增加剂量的前20周内。
绝大多数人的肠胃不适是轻微到中度的，但如果反应过于剧烈，就会演变成大麻烦。
真实案例：心脏骤停的险情 有一位57岁的女士，为了减肥，使用着每周15毫克（这是该药物的最高剂量）的替尔泊肽。在她的剂量被增加到15毫克后，她遭遇了极其严重的肠胃症状，经历了长时间的呕吐和腹泻。 你可以想象，身体里的水分和溶解在水里的“营养盐”随着呕吐物和排泄物大量流失。这导致她体内的电解质出现了极度危险的失衡：她的血钾降到了2.2（正常人的钾水平通常在3.5以上），镁离子降到了1.1。 缺钾和缺镁对心脏来说是致命的打击。这直接导致她出现了“心室颤动”（Ventricular Fibrillation）——这是一种非常可怕的心律失常，心脏的肌肉不再规律地泵血，而是像触电一样无效地疯狂颤抖，随后她发生了心脏骤停（也就是心脏不跳了）。幸运的是，医生通过紧急抢救和补充电解质，成功把她从鬼门关拉了回来。这个案例明确告诉我们，替尔泊肽引起的严重呕吐和腹泻，绝不是忍忍就过去的肠胃病，它可能会导致致命的电解质紊乱。
真实案例：急性肾损伤的教训 还有一位66岁的男性，体重高达160多斤（BMI指数高达61.4），因为要准备做减重手术而开始注射替尔泊肽。医生在4个月内把他的剂量从每周2.5毫克快速增加到了12.5毫克，这让他成功减掉了35公斤的体重。 但是，在手术前的检查中，医生发现他的肾脏出了大问题——他患上了“急性肾损伤”（Acute Kidney Injury，即肾脏突然失去了过滤血液中有毒废物的能力），并且体内的钾离子飙升到了6.8 mmol/L（血钾过高同样会引起心脏骤停），血液还呈现出代谢性酸中毒的状态。 医生分析，这很可能是因为药物引起的肠胃副作用导致他身体处于隐性的严重脱水状态，加上他本身有多种疾病并吃着多种药物，最终导致了肾脏和电解质的全面崩盘。经过在重症监护室（ICU）的抢救、补液和停用替尔泊肽，他的肾功能才得以恢复。
危机二：激素指令出错导致的“水中毒”（低钠血症）
除了肠胃副作用引发的连带反应，替尔泊肽还可能干扰身体对水分的调节机制。
我们的大脑里有一种激素叫做“抗利尿激素”，它的作用是告诉肾脏“把水分留在身体里，不要尿出去”。当这种激素分泌过多时，身体就会把大量的水分死死锁在血管里，这就叫“抗利尿激素分泌失调综合征”（SIADH）。水多了，血液里的盐分（特别是钠）就会被过度稀释，导致“低钠血症”，这就好比你往一碗咸汤里加了一大锅白开水，汤就没味道了。
钠是大脑神经细胞交流的关键物质。一旦血液里的钠浓度太低，脑细胞就会水肿，引发非常可怕的神经系统症状。
真实案例：用药4天后的癫痫发作 一位63岁、平时身体健康的女士，为了减肥开始注射替尔泊肽。仅仅在用药4天后，她突然发作了极其严重的全身抽搐（医学上叫强直阵挛性癫痫发作）。 送到医院一查，她的血钠浓度低到了可怕的122 mmol/L（正常值通常在135以上），尿液检查结果完全符合前面提到的“抗利尿激素分泌失调综合征”（SIADH）。医生没有发现她有其他任何可能导致这个问题的疾病。在停用替尔泊肽并严格限制她喝水后，她的钠水平慢慢回升，人也完全康复了。 这提醒大家，替尔泊肽有极少数情况下会直接引发身体激素指令错乱，导致严重的低钠血症，甚至引发抽搐。
危机三：药物“打架”引发的血钙飙升
有时候，电解质紊乱不是替尔泊肽一个人干的，而是它和其他药物“联手”造成的。
很多老年人或者高血压患者，会长期服用一种叫做“氢氯噻嗪”（Hydrochlorothiazide, 简称HCTZ）的降压药。这是一种利尿剂（让人多排尿的药），它的一个特点是会减少钙通过尿液排走，让更多的钙留在血液里。通常情况下，这并不会惹什么大祸。
但是，当氢氯噻嗪遇到替尔泊肽时，情况就变了。
真实案例：神志不清的高钙血症 一位65岁的肥胖女士，患有高血压、慢性肾病和2型糖尿病，她长期吃着氢氯噻嗪这种降压药。在开始注射替尔泊肽几天后，她突然变得神志不清、精神状态改变。 医生抽血一看，吓了一跳：她的校正血清钙浓度高达4.58 mmol/L（正常范围只有2.12到2.62 mmol/L）。血钙过高会让神经和肌肉的反应变得迟钝，导致极度疲惫、便秘、多尿，严重时大脑就会陷入糊涂状态。 医生排除了癌症等其他原因，认定这是两种药物发生了相互作用。替尔泊肽可能会增加骨骼细胞的活动，把骨头里的钙释放到血液里，而氢氯噻嗪又堵住了钙从尿液排出的通道，两者叠加，导致钙在血液里大爆炸。停用这两种药，并疯狂给她输液补充水分后，她的血钙在4天后恢复了正常。
危机四：盲目加量带来的多器官衰竭
很多人看到替尔泊肽强大的减肥效果（比如在72周的试验中，使用15毫克剂量的人平均减重高达20.9%），就会产生急于求成的心态，想要偷偷多打一点，或者不按医生的规定去迅速增加剂量。这种行为是极其危险的。
真实案例：重症监护室里的漫长康复 在英国，有一位39岁的健康男性，为了减肥私下开处方使用了替尔泊肽，并且在没有医生指导的情况下，非常快速地增加了药物剂量。 结果，他遭遇了生命危险。他出现了极其严重的低血糖、深度的电解质异常、全血细胞减少（也就是血液里的红细胞、白细胞、血小板全线崩溃），甚至还因为呕吐物吸入肺部导致了吸入性肺炎。最终，他的病情恶化成了呼吸衰竭、感染性休克和多器官功能障碍。他在重症监护室里躺了很久，不仅需要插管上呼吸机，还需要用机器代替肾脏洗血（肾脏替代疗法），甚至切开了气管，经历了非常复杂的神经系统康复才保住性命。
给普通人的大白话总结与建议
综合以上严谨的科学证据和医疗真实案例，我们可以得出一个非常清晰的结论：替尔泊肽确实存在导致电解质紊乱的风险。
虽然对于大部分人来说，只要在医生指导下正规使用，它引起的只是轻微的恶心或拉肚子；但如果掉以轻心，电解质紊乱可能会要了命。为了您的安全，请务必记住以下几点：
- 绝不求快，循序渐进： 替尔泊肽的剂量必须是从最小的剂量（比如2.5毫克）开始，慢慢让身体适应，按照医生的计划一点点往上加。绝对不能为了多掉几斤肉就自己盲目加大剂量，上述那个39岁小伙子的惨痛教训就是因为加药太猛。
- 拉肚子呕吐绝不是小事： 如果您在打针后出现了严重的、持续不停的呕吐或者拉肚子，千万不要觉得“拉得越多瘦得越快”。这会让你的身体脱水，流失维持心脏跳动的钾和镁。这个时候必须立刻去医院检查电解质并补充水分，否则随时可能引发心脏骤停。
- 注意您的其他常用药： 如果您本身患有高血压、肾病，并且正在吃降压药（特别是像“氢氯噻嗪”这种利尿剂），或者吃着降糖的胰岛素，在开始打替尔泊肽的头一两周，一定要去医院抽血复查一下您的血钙、血钾等电解质水平和肾功能。
- 警惕异常的神经症状： 如果打药后突然出现极度的虚弱、精神恍惚、说话颠三倒四，甚至是莫名其妙的抽搐，这很可能是因为钠离子太低或者钙离子太高让大脑“短路”了，请立即拨打急救电话。
科学在进步，替尔泊肽确实是治疗糖尿病和肥胖的有力武器，在三年的随访研究中也证实了它能显著延缓糖尿病的发生。但任何强大的武器都有后坐力，只有了解风险、敬畏医学、听从专业医生的指导，我们才能安全地享受科学带来的红利。
References
1A potential association between tirzepatide and hypercalcemia in the setting of chronic hydrochlorothiazide use.PubMed
Basil Nduma, Sai Nikhitha Malapati, Veeranna Vibhuti
Endocrinol Diabetes Metab Case Rep. 2025 Sep 5;2025(3). doi: 10.1530/EDM-25-0067. Print 2025 Jul 1.
SUMMARY: Hypercalcemia is a prevalent electrolyte disturbance commonly associated with primary hyperparathyroidism, cancer, or medication adverse effects. Thiazide diuretics reduce urinary calcium excretion, increasing calcium reabsorption and hypercalcemia. Tirzepatide, a dual GIP and GLP-1 receptor agonist, is increasingly used for type 2 diabetes and obesity. While GIP/GLP-1 agonists typically have negligible effects on calcium homeostasis, the interaction between tirzepatide and thiazides remains unstudied. We report a 65-year-old female with obesity, hypertension, CKD3, and T2DM on chronic HCTZ who developed symptomatic hypercalcemia (corrected calcium: 4.58 mmol/L; normal range: 2.12-2.62 mmol/L), resulting in altered mental status days after initiating tirzepatide. PTH and vitamin D levels were low, and imaging ruled out malignancy. Discontinuation of tirzepatide/HCTZ, IV hydration, and calcitonin normalized her calcium by hospital day 4. This case highlights a potential association between HCTZ and tirzepatide in causing severe hypercalcemia. No prior reports link tirzepatide (or its combination with thiazides) to hypercalcemia. The mechanism likely involves thiazide-induced calcium reabsorption and tirzepatide's effects on bone turnover. As the use of tirzepatide and other GLP-1/GIP agonists becomes more prevalent, clinicians need to closely monitor calcium levels in thiazide-treated individuals, particularly those with CKD. Additional research is also needed to elucidate the drug's interaction with calcium metabolism. LEARNING POINTS: Clinicians should be aware of the potential for severe hypercalcemia when tirzepatide is co-administered with chronic thiazide diuretics, particularly hydrochlorothiazide (HCTZ), in patients with pre-existing CKD. Tirzepatide, a dual GIP and GLP-1 receptor agonist, may influence calcium metabolism through mechanisms including increased osteoblastic activity and altered PTH regulation, especially in individuals with impaired renal clearance. Baseline and follow-up serum calcium monitoring is strongly recommended within 1-2 weeks of initiating tirzepatide in patients receiving thiazide diuretics or those with CKD. This case suggests a possible drug-drug interaction between tirzepatide and HCTZ leading to symptomatic hypercalcemia, highlighting the need for pharmacovigilance as newer agents are integrated into routine diabetes care. Severe hypercalcemia can present with nonspecific symptoms such as altered mental status, fatigue, constipation, and polyuria; clinicians should maintain a high index of suspicion in susceptible populations. Prompt cessation of the suspected offending agents, hydration, and short-term use of calcitonin can result in rapid and sustained normalization of calcium levels without the need for bisphosphonates.
2Life-Threatening Ventricular Fibrillation Linked to High-Dose Tirzepatide-Induced Gastrointestinal Side Effects.PubMed
Thirumala Keerthi Chandrika Kammaripalle, Jacob R Giordano, Humza Rana, et al.
Cureus. 2025 Jun 4;17(6):e85366. doi: 10.7759/cureus.85366. eCollection 2025 Jun.
Tirzepatide is a long-acting agonist of glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptors, used for the treatment of type 2 diabetes and obesity, and recently approved for obstructive sleep apnea. It is known to cause gastrointestinal (GI) side effects; however, these are generally not severe enough to be life-threatening. We present a unique case of a 57-year-old woman with no prior cardiac history who was on a high dose of tirzepatide (15 mg weekly) for weight loss. After her dose was increased to 15 mg, she developed severe GI symptoms, including prolonged vomiting and diarrhea, leading to profound electrolyte imbalances (K⁺ 2.2, Mg²⁺ 1.1, and corrected Ca²⁺ 5.6) and ultimately resulting in ventricular fibrillation and cardiac arrest. The patient was successfully resuscitated and stabilized with electrolyte correction. A comprehensive evaluation, including left heart catheterization, ruled out obstructive coronary artery disease. Following the cardiac arrest, the patient had severely reduced left ventricular function, likely due to hypoxia and post-cardiac arrest stunning. However, her ejection fraction significantly improved within a few weeks, suggesting that tirzepatide-associated GI side effects and subsequent electrolyte disturbances were the primary precipitating factors. This case highlights a previously undocumented risk of life-threatening arrhythmias due to severe electrolyte disturbances caused by tirzepatide-induced GI side effects. Vigilant electrolyte monitoring is crucial, particularly in patients on high doses or those with additional risk factors.
3Continued Treatment With Tirzepatide for Maintenance of Weight Reduction in Adults With Obesity: The SURMOUNT-4 Randomized Clinical Trial.PubMed
Louis J Aronne, Naveed Sattar, Deborah B Horn, et al.
JAMA. 2024 Jan 2;331(1):38-48. doi: 10.1001/jama.2023.24945.
IMPORTANCE: The effect of continued treatment with tirzepatide on maintaining initial weight reduction is unknown. OBJECTIVE: To assess the effect of tirzepatide, with diet and physical activity, on the maintenance of weight reduction. DESIGN, SETTING, AND PARTICIPANTS: This phase 3, randomized withdrawal clinical trial conducted at 70 sites in 4 countries with a 36-week, open-label tirzepatide lead-in period followed by a 52-week, double-blind, placebo-controlled period included adults with a body mass index greater than or equal to 30 or greater than or equal to 27 and a weight-related complication, excluding diabetes. INTERVENTIONS: Participants (n = 783) enrolled in an open-label lead-in period received once-weekly subcutaneous maximum tolerated dose (10 or 15 mg) of tirzepatide for 36 weeks. At week 36, a total of 670 participants were randomized (1:1) to continue receiving tirzepatide (n = 335) or switch to placebo (n = 335) for 52 weeks. MAIN OUTCOMES AND MEASURES: The primary end point was the mean percent change in weight from week 36 (randomization) to week 88. Key secondary end points included the proportion of participants at week 88 who maintained at least 80% of the weight loss during the lead-in period. RESULTS: Participants (n = 670; mean age, 48 years; 473 [71%] women; mean weight, 107.3 kg) who completed the 36-week lead-in period experienced a mean weight reduction of 20.9%. The mean percent weight change from week 36 to week 88 was -5.5% with tirzepatide vs 14.0% with placebo (difference, -19.4% [95% CI, -21.2% to -17.7%]; P < .001). Overall, 300 participants (89.5%) receiving tirzepatide at 88 weeks maintained at least 80% of the weight loss during the lead-in period compared with 16.6% receiving placebo (P < .001). The overall mean weight reduction from week 0 to 88 was 25.3% for tirzepatide and 9.9% for placebo. The most common adverse events were mostly mild to moderate gastrointestinal events, which occurred more commonly with tirzepatide vs placebo. CONCLUSIONS AND RELEVANCE: In participants with obesity or overweight, withdrawing tirzepatide led to substantial regain of lost weight, whereas continued treatment maintained and augmented initial weight reduction. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04660643.
4Tirzepatide-Associated Euglycemic Diabetic Ketoacidosis in the Absence of Sodium-Glucose Cotransporter-2 Inhibitor Use: A Case Report.PubMed
Christina Campana, Ashley Heaney, Negin Ceraolo, et al.
J Emerg Med. 2026 Apr;83:57-60. doi: 10.1016/j.jemermed.2026.01.002. Epub 2026 Jan 31.
BACKGROUND: Euglycemic diabetic ketoacidosis (EDKA) is most commonly associated with sodium-glucose cotransporter-2 (SGLT2) inhibitors. However, emerging evidence suggests that glucagon-like peptide-1 (GLP-1) receptor agonists and dual incretin agents such as tirzepatide (Mounjaro) may also precipitate EDKA, though reports remain rare. CASE REPORT: We report a case of EDKA in a patient on tirzepatide monotherapy, with no concurrent SGLT2 inhibitor use. The patient presented with nausea, vomiting, and abdominal pain. Laboratory evaluation revealed a severe anion gap metabolic acidosis (CO₂ 7 mmol/L, anion gap 28, pH 7.1) and ketonuria, with mild hyperglycemia (glucose 167 mg/dL). The patient was managed with intravenous fluids, dextrose, and insulin infusion per standard diabetic ketoacidosis protocol, resulting in resolution of the anion gap. STUDY OBJECTIVE: This case highlights a potential association between tirzepatide and EDKA, possibly related to mechanisms involving starvation ketosis and reduced insulin availability. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Emergency physicians should consider EDKA in patients taking incretin-based therapies such as tirzepatide who present with metabolic acidosis and ketosis in the absence of significant hyperglycemia.
5Tirzepatide-Induced Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH) Presenting With Seizures.PubMed
Islam Shah, Devesh Sennik, Fahas Ali Vattiyam Veettil
JCEM Case Rep. 2025 Oct 31;3(12):luaf261. doi: 10.1210/jcemcr/luaf261. eCollection 2025 Dec.
Tirzepatide (Mounjaro), a novel, dual glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonist, is increasingly prescribed for type 2 diabetes and off-label weight loss. While gastrointestinal adverse effects are common, hyponatremia induced by tirzepatide is rarely reported. We report a 63-year-old woman with no significant past medical history who developed tonic-clonic seizures 4 days after starting tirzepatide for weight loss. Laboratory evaluation revealed severe hyponatremia (serum sodium 122 mmol/L), low serum osmolality, and high urine osmolality and urine sodium consistent with syndrome of inappropriate antidiuretic hormone secretion (SIADH). No other causes were identified. Discontinuation of tirzepatide and fluid restriction led to gradual normalization of sodium levels and full clinical recovery. This case highlights tirzepatide as a potential cause of SIADH and severe hyponatremia leading to seizures, even in low-risk individuals. Clinicians should monitor electrolytes when initiating GLP-1 receptor agonists, especially off-label.
6Severe Adverse Effects of Tirzepatide Overdose Requiring Intensive Care Unit Admission and Complex Rehabilitation.PubMed
Mahmoud Sharafeldin, Noor Alhamdan, Ayesha Khaliq
Cureus. 2025 Dec 8;17(12):e98681. doi: 10.7759/cureus.98681. eCollection 2025 Dec.
Tirzepatide, a dual glucagon-like peptide-1 (GLP-1)/glucose-dependent insulinotropic polypeptide receptor agonist, is increasingly prescribed privately in the United Kingdom for weight loss. While gastrointestinal side effects are well recognized, severe metabolic derangements and hematological complications remain rarely documented. We report the case of a 39-year-old man with no significant comorbidities who developed life-threatening hypoglycemia, profound electrolyte abnormalities, pancytopenia, and aspiration pneumonia following unsupervised rapid dose escalation of tirzepatide used for weight loss. His clinical course was complicated by respiratory failure, septic shock, multiorgan dysfunction, and prolonged intensive care unit stay requiring mechanical ventilation, renal replacement therapy, tracheostomy, and complex neurorehabilitation. This case highlights the critical complications associated with inappropriate tirzepatide dosing and underscores the need for clinician vigilance and patient education as GLP-1 receptor agonist use continues to rise in the community.
7Tirzepatide Once Weekly for the Treatment of Obesity.PubMed
Ania M Jastreboff, Louis J Aronne, Nadia N Ahmad, et al.
N Engl J Med. 2022 Jul 21;387(3):205-216. doi: 10.1056/NEJMoa2206038. Epub 2022 Jun 4.
BACKGROUND: Obesity is a chronic disease that results in substantial global morbidity and mortality. The efficacy and safety of tirzepatide, a novel glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptor agonist, in people with obesity are not known. METHODS: In this phase 3 double-blind, randomized, controlled trial, we assigned 2539 adults with a body-mass index (BMI; the weight in kilograms divided by the square of the height in meters) of 30 or more, or 27 or more and at least one weight-related complication, excluding diabetes, in a 1:1:1:1 ratio to receive once-weekly, subcutaneous tirzepatide (5 mg, 10 mg, or 15 mg) or placebo for 72 weeks, including a 20-week dose-escalation period. Coprimary end points were the percentage change in weight from baseline and a weight reduction of 5% or more. The treatment-regimen estimand assessed effects regardless of treatment discontinuation in the intention-to-treat population. RESULTS: At baseline, the mean body weight was 104.8 kg, the mean BMI was 38.0, and 94.5% of participants had a BMI of 30 or higher. The mean percentage change in weight at week 72 was -15.0% (95% confidence interval [CI], -15.9 to -14.2) with 5-mg weekly doses of tirzepatide, -19.5% (95% CI, -20.4 to -18.5) with 10-mg doses, and -20.9% (95% CI, -21.8 to -19.9) with 15-mg doses and -3.1% (95% CI, -4.3 to -1.9) with placebo (P<0.001 for all comparisons with placebo). The percentage of participants who had weight reduction of 5% or more was 85% (95% CI, 82 to 89), 89% (95% CI, 86 to 92), and 91% (95% CI, 88 to 94) with 5 mg, 10 mg, and 15 mg of tirzepatide, respectively, and 35% (95% CI, 30 to 39) with placebo; 50% (95% CI, 46 to 54) and 57% (95% CI, 53 to 61) of participants in the 10-mg and 15-mg groups had a reduction in body weight of 20% or more, as compared with 3% (95% CI, 1 to 5) in the placebo group (P<0.001 for all comparisons with placebo). Improvements in all prespecified cardiometabolic measures were observed with tirzepatide. The most common adverse events with tirzepatide were gastrointestinal, and most were mild to moderate in severity, occurring primarily during dose escalation. Adverse events caused treatment discontinuation in 4.3%, 7.1%, 6.2%, and 2.6% of participants receiving 5-mg, 10-mg, and 15-mg tirzepatide doses and placebo, respectively. CONCLUSIONS: In this 72-week trial in participants with obesity, 5 mg, 10 mg, or 15 mg of tirzepatide once weekly provided substantial and sustained reductions in body weight. (Supported by Eli Lilly; SURMOUNT-1 ClinicalTrials.gov number, NCT04184622.).
8Severe diabetic ketoacidosis associated with insulin dose reduction after tirzepatide initiation.PubMed
Ei Thinzar Aung, Thinzar Min, Ye Thurein Mon, et al.
BMJ Case Rep. 2026 Mar 9;19(3):e270158. doi: 10.1136/bcr-2025-270158.
A man in his 50s with insulin-treated type 2 diabetes mellitus presented with a 1-day history of severe abdominal pain, nausea and vomiting, 15 days after initiation of tirzepatide. On admission, he was severely dehydrated with profound high-anion gap metabolic acidosis (pH 6.8), marked hyperglycaemia and ketosis, consistent with severe diabetic ketoacidosis (DKA), requiring intensive therapy unit admission. He had been treated with insulin for over 10 years, with preserved renal function (estimated glomerular filtration rate 80 mL/min/1.73 m), haemoglobin A1c of 61 mmol/mol and no previous history of DKA. Tirzepatide 2.5 mg once a week was commenced, and a telephone review 6 days after the first dose confirmed mild bloating with preserved oral intake and continued insulin use. Following the second dose, gastrointestinal symptoms progressed, resulting in complete inability to tolerate food or fluids for 24 hours prior to admission. During this period, the patient reduced his basal insulin glargine dose from 40 to 20 units for 3 days due to fear of hypoglycaemia. This case highlights the importance of reinforcing sick-day rules and continuation of basal insulin when initiating tirzepatide in insulin-treated patients.
9Acute Kidney Injury After Accelerated Dosing of Tirzepatide in a Patient with Multiple Comorbidities: A Case Report.PubMed
Abdulelah H Almansour
Am J Case Rep. 2025 Dec 6;26:e950781. doi: 10.12659/AJCR.950781.
BACKGROUND Tirzepatide is effective for glycemic control and weight management in type 2 diabetes and obesity. Clinical trials have demonstrated tirzepatide's lower risk of acute kidney injury (AKI) compared with existing glucagon-like peptide-1 receptor agonists, along with benefits including reduced albuminuria and stable estimated glomerular filtration rate. Rare cases of AKI have been reported, potentially associated with dehydration from gastrointestinal side effects, polypharmacy, or comorbidities. We describe AKI in a non-diabetic, multimorbid patient after rapid tirzepatide dose escalation, underscoring the importance of identifying susceptible patient phenotypes. CASE REPORT A 66-year-old man with morbid obesity (body mass index 61.4 kg/m²), hypertension, prediabetes, hypothyroidism, and polypharmacy presented for weight management before bariatric surgery. Tirzepatide was initiated at 2.5 mg weekly and escalated to 12.5 mg over 4 months, resulting in weight loss of 35 kg. Preoperative evaluation revealed AKI, with a serum creatinine level of 2.4 mg/dL, potassium of 6.8 mmol/L, and metabolic acidosis (pH 7.31). Potential contributors included pharmacodynamic interactions with antihypertensive agents or dehydration secondary to gastrointestinal side effects. Management involved intensive care unit admission, antihyperkalemic therapy, intravenous fluids, and tirzepatide discontinuation. Renal function improved (creatinine 1.18 mg/dL) by discharge. CONCLUSIONS The AKI in this case may have resulted from the combination of rapid tirzepatide dose escalation, polypharmacy, and multimorbidity, potentially compounded by subclinical volume depletion or hemodynamic alterations. Clinicians should utilize standard titration schedules, closely monitor blood pressure and renal function, and exercise caution in patients with complex medication regimens to maximize tirzepatide's therapeutic benefits while minimizing renal risk.
10Tirzepatide for the Treatment of Obstructive Sleep Apnea and Obesity.PubMed
Atul Malhotra, Ronald R Grunstein, Ingo Fietze, et al.
N Engl J Med. 2024 Oct 3;391(13):1193-1205. doi: 10.1056/NEJMoa2404881. Epub 2024 Jun 21.
BACKGROUND: Obstructive sleep apnea is characterized by disordered breathing during sleep and is associated with major cardiovascular complications; excess adiposity is an etiologic risk factor. Tirzepatide may be a potential treatment. METHODS: We conducted two phase 3, double-blind, randomized, controlled trials involving adults with moderate-to-severe obstructive sleep apnea and obesity. Participants who were not receiving treatment with positive airway pressure (PAP) at baseline were enrolled in trial 1, and those who were receiving PAP therapy at baseline were enrolled in trial 2. The participants were assigned in a 1:1 ratio to receive either the maximum tolerated dose of tirzepatide (10 mg or 15 mg) or placebo for 52 weeks. The primary end point was the change in the apnea-hypopnea index (AHI, the number of apneas and hypopneas during an hour of sleep) from baseline. Key multiplicity-controlled secondary end points included the percent change in AHI and body weight and changes in hypoxic burden, patient-reported sleep impairment and disturbance, high-sensitivity C-reactive protein (hsCRP) concentration, and systolic blood pressure. RESULTS: At baseline, the mean AHI was 51.5 events per hour in trial 1 and 49.5 events per hour in trial 2, and the mean body-mass index (BMI, the weight in kilograms divided by the square of the height in meters) was 39.1 and 38.7, respectively. In trial 1, the mean change in AHI at week 52 was -25.3 events per hour (95% confidence interval [CI], -29.3 to -21.2) with tirzepatide and -5.3 events per hour (95% CI, -9.4 to -1.1) with placebo, for an estimated treatment difference of -20.0 events per hour (95% CI, -25.8 to -14.2) (P<0.001). In trial 2, the mean change in AHI at week 52 was -29.3 events per hour (95% CI, -33.2 to -25.4) with tirzepatide and -5.5 events per hour (95% CI, -9.9 to -1.2) with placebo, for an estimated treatment difference of -23.8 events per hour (95% CI, -29.6 to -17.9) (P<0.001). Significant improvements in the measurements for all prespecified key secondary end points were observed with tirzepatide as compared with placebo. The most frequently reported adverse events with tirzepatide were gastrointestinal in nature and mostly mild to moderate in severity. CONCLUSIONS: Among persons with moderate-to-severe obstructive sleep apnea and obesity, tirzepatide reduced the AHI, body weight, hypoxic burden, hsCRP concentration, and systolic blood pressure and improved sleep-related patient-reported outcomes. (Funded by Eli Lilly; SURMOUNT-OSA ClinicalTrials.gov number, NCT05412004.).
11Tirzepatide for Obesity Treatment and Diabetes Prevention.PubMed
Ania M Jastreboff, Carel W le Roux, Adam Stefanski, et al.
N Engl J Med. 2025 Mar 6;392(10):958-971. doi: 10.1056/NEJMoa2410819. Epub 2024 Nov 13.
BACKGROUND: Obesity is a chronic disease and causal precursor to myriad other conditions, including type 2 diabetes. In an earlier analysis of the SURMOUNT-1 trial, tirzepatide was shown to provide substantial and sustained reductions in body weight in persons with obesity over a 72-week period. Here, we report the 3-year safety outcomes with tirzepatide and its efficacy in reducing weight and delaying progression to type 2 diabetes in persons with both obesity and prediabetes. METHODS: We performed a phase 3, double-blind, randomized, controlled trial in which 2539 participants with obesity, of whom 1032 also had prediabetes, were assigned in a 1:1:1:1 ratio to receive tirzepatide at a once-weekly dose of 5 mg, 10 mg, or 15 mg or placebo. The current analysis involved the participants with both obesity and prediabetes, who received their assigned dose of tirzepatide or placebo for a total of 176 weeks, followed by a 17-week off-treatment period. The three key secondary end points, which were controlled for type I error, were the percent change in body weight from baseline to week 176 and onset of type 2 diabetes during the 176-week and 193-week periods. RESULTS: At 176 weeks, the mean percent change in body weight among the participants who received tirzepatide was -12.3% with the 5-mg dose, -18.7% with the 10-mg dose, and -19.7% with the 15-mg dose, as compared with -1.3% among those who received placebo (P<0.001 for all comparisons with placebo). Fewer participants received a diagnosis of type 2 diabetes in the tirzepatide groups than in the placebo group (1.3% vs. 13.3%; hazard ratio, 0.07; 95% confidence interval [CI], 0.0 to 0.1; P<0.001). After 17 weeks off treatment or placebo, 2.4% of the participants who received tirzepatide and 13.7% of those who received placebo had type 2 diabetes (hazard ratio, 0.12; 95% CI, 0.1 to 0.2; P<0.001). Other than coronavirus disease 2019, the most common adverse events were gastrointestinal, most of which were mild to moderate in severity and occurred primarily during the dose-escalation period in the first 20 weeks of the trial. No new safety signals were identified. CONCLUSIONS: Three years of treatment with tirzepatide in persons with obesity and prediabetes resulted in substantial and sustained weight reduction and a markedly lower risk of progression to type 2 diabetes than that with placebo. (Funded by Eli Lilly; SURMOUNT-1 ClinicalTrials.gov number, NCT04184622.).
12Tirzepatide versus Semaglutide Once Weekly in Patients with Type 2 Diabetes.PubMed
Juan P Frías, Melanie J Davies, Julio Rosenstock, et al.
N Engl J Med. 2021 Aug 5;385(6):503-515. doi: 10.1056/NEJMoa2107519. Epub 2021 Jun 25.
BACKGROUND: Tirzepatide is a dual glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 (GLP-1) receptor agonist that is under development for the treatment of type 2 diabetes. The efficacy and safety of once-weekly tirzepatide as compared with semaglutide, a selective GLP-1 receptor agonist, are unknown. METHODS: In an open-label, 40-week, phase 3 trial, we randomly assigned 1879 patients, in a 1:1:1:1 ratio, to receive tirzepatide at a dose of 5 mg, 10 mg, or 15 mg or semaglutide at a dose of 1 mg. At baseline, the mean glycated hemoglobin level was 8.28%, the mean age 56.6 years, and the mean weight 93.7 kg. The primary end point was the change in the glycated hemoglobin level from baseline to 40 weeks. RESULTS: The estimated mean change from baseline in the glycated hemoglobin level was -2.01 percentage points, -2.24 percentage points, and -2.30 percentage points with 5 mg, 10 mg, and 15 mg of tirzepatide, respectively, and -1.86 percentage points with semaglutide; the estimated differences between the 5-mg, 10-mg, and 15-mg tirzepatide groups and the semaglutide group were -0.15 percentage points (95% confidence interval [CI], -0.28 to -0.03; P = 0.02), -0.39 percentage points (95% CI, -0.51 to -0.26; P<0.001), and -0.45 percentage points (95% CI, -0.57 to -0.32; P<0.001), respectively. Tirzepatide at all doses was noninferior and superior to semaglutide. Reductions in body weight were greater with tirzepatide than with semaglutide (least-squares mean estimated treatment difference, -1.9 kg, -3.6 kg, and -5.5 kg, respectively; P<0.001 for all comparisons). The most common adverse events were gastrointestinal and were primarily mild to moderate in severity in the tirzepatide and semaglutide groups (nausea, 17 to 22% and 18%; diarrhea, 13 to 16% and 12%; and vomiting, 6 to 10% and 8%, respectively). Of the patients who received tirzepatide, hypoglycemia (blood glucose level, <54 mg per deciliter) was reported in 0.6% (5-mg group), 0.2% (10-mg group), and 1.7% (15-mg group); hypoglycemia was reported in 0.4% of those who received semaglutide. Serious adverse events were reported in 5 to 7% of the patients who received tirzepatide and in 3% of those who received semaglutide. CONCLUSIONS: In patients with type 2 diabetes, tirzepatide was noninferior and superior to semaglutide with respect to the mean change in the glycated hemoglobin level from baseline to 40 weeks. (Funded by Eli Lilly; SURPASS-2 ClinicalTrials.gov number, NCT03987919.).
13Semaglutide vs Tirzepatide for Weight Loss in Adults With Overweight or Obesity.PubMed
Patricia J Rodriguez, Brianna M Goodwin Cartwright, Samuel Gratzl, et al.
JAMA Intern Med. 2024 Sep 1;184(9):1056-1064. doi: 10.1001/jamainternmed.2024.2525.
IMPORTANCE: Although tirzepatide and semaglutide were shown to reduce weight in randomized clinical trials, data from head-to-head comparisons in populations with overweight or obesity are not yet available. OBJECTIVE: To compare on-treatment weight loss and rates of gastrointestinal adverse events (AEs) among adults with overweight or obesity receiving tirzepatide or semaglutide labeled for type 2 diabetes (T2D) in a clinical setting. DESIGN, SETTING, AND PARTICIPANTS: In this cohort study, adults with overweight or obesity receiving semaglutide or tirzepatide between May 2022 and September 2023 were identified using electronic health record (EHR) data linked to dispensing information from a collective of US health care systems. On-treatment weight outcomes through November 3, 2023, were assessed. Adults with overweight or obesity and regular care in the year before initiation, no prior glucagon-like peptide 1 receptor agonist receptor agonist use, a prescription within 60 days prior to initiation, and an available baseline weight were identified. The analysis was completed on April 3, 2024. EXPOSURES: Tirzepatide or semaglutide in formulations labeled for T2D, on or off label. MAIN OUTCOMES AND MEASURES: On-treatment weight change in a propensity score-matched population, assessed as hazard of achieving 5% or greater, 10% or greater, and 15% or greater weight loss, and percentage change in weight at 3, 6, and 12 months. Hazards of gastrointestinal AEs were compared. RESULTS: Among 41 222 adults meeting the study criteria (semaglutide, 32 029; tirzepatide, 9193), 18 386 remained after propensity score matching. The mean (SD) age was 52.0 (12.9) years, 12 970 were female (70.5%), 14 182 were white (77.1%), 2171 Black (11.8%), 354 Asian (1.9%), 1679 were of other or unknown race, and 9563 (52.0%) had T2D. The mean (SD) baseline weight was 110 (25.8) kg. Follow-up was ended by discontinuation for 5140 patients (55.9%) receiving tirzepatide and 4823 (52.5%) receiving semaglutide. Patients receiving tirzepatide were significantly more likely to achieve weight loss (≥5%; hazard ratio [HR], 1.76, 95% CI, 1.68, 1.84; ≥10%; HR, 2.54; 95% CI, 2.37, 2.73; and ≥15%; HR, 3.24; 95% CI, 2.91, 3.61). On-treatment changes in weight were larger for patients receiving tirzepatide at 3 months (difference, -2.4%; 95% CI -2.5% to -2.2%), 6 months (difference, -4.3%; 95% CI, -4.7% to -4.0%), and 12 months (difference, -6.9%; 95% CI, -7.9% to -5.8%). Rates of gastrointestinal AEs were similar between groups. CONCLUSIONS AND RELEVANCE: In this population of adults with overweight or obesity, use of tirzepatide was associated with significantly greater weight loss than semaglutide. Future study is needed to understand differences in other important outcomes.
14Comparative effectiveness of GLP-1 receptor agonists on glycaemic control, body weight, and lipid profile for type 2 diabetes: systematic review and network meta-analysis.PubMed
Haiqiang Yao, Anqi Zhang, Delong Li, et al.
BMJ. 2024 Jan 29;384:e076410. doi: 10.1136/bmj-2023-076410.
OBJECTIVE: To evaluate the comparative efficacy and safety of glucagon-like peptide-1 receptor agonists (GLP-1RAs) on glycaemic control, body weight, and lipid profile in adults with type 2 diabetes. DESIGN: Systematic review and network meta-analysis. DATA SOURCES: PubMed, Web of Science, Cochrane Central Register of Controlled Trials (CENTRAL), and Embase from database inception to 19 August 2023. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Eligible randomised controlled trials enrolled adults with type 2 diabetes who received GLP-1RA treatments and compared effects with placebo or any GLP-1RA drug, with a follow-up duration of at least 12 weeks. Trials with a crossover design, non-inferiority studies comparing GLP-1RA and other drug classes without a placebo group, using withdrawn drugs, and non-English studies were deemed ineligible. RESULTS: 76 eligible trials involving 15 GLP-1RA drugs and 39 246 participants were included in this network meta-analysis; all subsequent estimates refer to the comparison with placebo. All 15 GLP-1RAs effectively lowered haemoglobin A and fasting plasma glucose concentrations. Tirzepatide induced the largest reduction of haemoglobin A concentrations (mean difference -2.10% (95% confidence interval -2.47% to -1.74%), surface under the cumulative ranking curve 94.2%; high confidence of evidence), and fasting plasma glucose concentrations (-3.12 mmol/L (-3.59 to -2.66), 97.2%; high confidence), and proved the most effective GLP-1RA drug for glycaemic control. Furthermore, GLP-1RAs were shown to have strong benefits to weight management for patients with type 2 diabetes. CagriSema (semaglutide with cagrilintide) resulted in the highest weight loss (mean difference -14.03 kg (95% confidence interval -17.05 to -11.00); high confidence of evidence), followed by tirzepatide (-8.47 kg (-9.68 to -7.26); high confidence). Semaglutide was effective in lowering the concentration of low density lipoprotein (-0.16 mmol/L (-0.30 to -0.02)) and total cholesterol (-0.48 mmol/L (-0.84 to -0.11)). Moreover, this study also raises awareness of gastrointestinal adverse events induced by GLP-1RAs, and concerns about safety are especially warranted for high dose administration. CONCLUSIONS: GLP-1RAs are efficacious in treating adults with type 2 diabetes. Compared with the placebo, tirzepatide was the most effective GLP-1RA drug for glycaemic control by reducing haemoglobin A and fasting plasma glucose concentrations. GLP-1RAs also significantly improved weight management for type 2 diabetes, with CagriSema performing the best for weight loss. The results prompt safety concerns for GLP-1RAs, especially with high dose administration, regarding gastrointestinal adverse events. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42022342845.
15Tirzepatide once weekly for the treatment of obesity in people with type 2 diabetes (SURMOUNT-2): a double-blind, randomised, multicentre, placebo-controlled, phase 3 trial.PubMed
W Timothy Garvey, Juan P Frias, Ania M Jastreboff, et al.
Lancet. 2023 Aug 19;402(10402):613-626. doi: 10.1016/S0140-6736(23)01200-X. Epub 2023 Jun 26.
BACKGROUND: Weight reduction is essential for improving health outcomes in people with obesity and type 2 diabetes. We assessed the efficacy and safety of tirzepatide, a glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptor agonist, versus placebo, for weight management in people living with obesity and type 2 diabetes. METHODS: This phase 3, double-blind, randomised, placebo-controlled trial was conducted in seven countries. Adults (aged ≥18 years) with a body-mass index (BMI) of 27 kg/m or higher and glycated haemoglobin (HbA) of 7-10% (53-86 mmol/mol) were randomly assigned (1:1:1), using a computer-generated random sequence via a validated interactive web-response system, to receive either once-weekly, subcutaneous tirzepatide (10 mg or 15 mg) or placebo for 72 weeks. All participants, investigators, and the sponsor were masked to treatment assignment. Coprimary endpoints were the percent change in bodyweight from baseline and bodyweight reduction of 5% or higher. The treatment-regimen estimand assessed effects regardless of treatment discontinuation or initiation of antihyperglycaemic rescue therapy. Efficacy and safety endpoints were analysed with data from all randomly assigned participants (intention-to-treat population). This trial is registered with ClinicalTrials.gov, NCT04657003. FINDINGS: Between March 29, 2021, and April 10, 2023, of 1514 adults assessed for eligibility, 938 (mean age 54·2 years [SD 10·6], 476 [51%] were female, 710 [76%] were White, and 561 [60%] were Hispanic or Latino) were randomly assigned and received at least one dose of tirzepatide 10 mg (n=312), tirzepatide 15 mg (n=311), or placebo (n=315). Baseline mean bodyweight was 100·7 kg (SD 21·1), BMI 36·1 kg/m (SD 6·6), and HbA 8·02% (SD 0·89; 64·1 mmol/mol [SD 9·7]). Least-squares mean change in bodyweight at week 72 with tirzepatide 10 mg and 15 mg was -12·8% (SE 0·6) and -14·7% (0·5), respectively, and -3·2% (0·5) with placebo, resulting in estimated treatment differences versus placebo of -9·6% percentage points (95% CI -11·1 to -8·1) with tirzepatide 10 mg and -11·6% percentage points (-13·0 to -10·1) with tirzepatide 15 mg (all p<0·0001). More participants treated with tirzepatide versus placebo met bodyweight reduction thresholds of 5% or higher (79-83% vs 32%). The most frequent adverse events with tirzepatide were gastrointestinal-related, including nausea, diarrhoea, and vomiting and were mostly mild to moderate in severity, with few events leading to treatment discontinuation (<5%). Serious adverse events were reported by 68 (7%) participants overall and two deaths occurred in the tirzepatide 10 mg group, but deaths were not considered to be related to the study treatment by the investigator. INTERPRETATION: In this 72-week trial in adults living with obesity and type 2 diabetes, once-weekly tirzepatide 10 mg and 15 mg provided substantial and clinically meaningful reduction in bodyweight, with a safety profile that was similar to other incretin-based therapies for weight management. FUNDING: Eli Lilly and Company.