在2026年欧洲肝病学会年会（EASL 2026）上，克罗地亚里耶卡大学医学院（Faculty of Medicine, University of Rijeka）Sanja Klobucar教授带来专题报告，聚焦药物不良反应管理与患者用药依从性两大临床重点。如今新一代肠促胰素类药物为肥胖及相关疾病治疗带来全新突破，也推动了临床诊疗格局的革新。但在实际诊疗过程中，各类用药误区、药物不耐受以及患者提前停药等问题，不断影响着MASLD的整体治疗效果。Klobucar教授结合临床实践，分享了兼顾不良反应防控与患者依从性提升的创新管理思路，为优化MASLD全病程诊疗结局提供了实用参考。

《国际肝病》

目前临床实际诊疗里，医生容易陷入哪些用药误区？您认为应该如何优化MASLD整体诊疗结局？

Sanja Klobucar教授：以司美格鲁肽、替尔泊肽为代表的新一代肠促胰素类药物，彻底改变了肥胖的临床管理模式。这类药物减重效果可媲美减重手术，还能为患者带来多重健康获益，有效改善生活质量。

但该类药物疗效依赖长期持续用药，过早停药会大幅削弱治疗效果。临床数据显示，超半数患者会在用药1年内终止治疗，药物不良反应是早期停药的首要原因，因此建立完善的不良反应预防与应对策略，是保障疗效的关键。

对此，临床可采用简洁实用的3Es管理框架，即宣教与讲解说明（educate and explain）、调整饮食模式（eat differently）、缓慢加量（escalate slowly）。启动药物治疗前，临床需对患者开展充分宣教，详细说明药物使用方法、治疗预期、不良反应及对应处理方式，同时告知患者，该类药物的不良反应多为轻中度、一过性症状，均可有效管控，缓解患者顾虑。

该类药物的不良反应以胃肠道症状为主，包括恶心、呕吐、腹泻、便秘等，患者可通过调整饮食方式与食物选择减少不适症状。在饮食习惯上，需指导患者细嚼慢咽、少食多餐、控制进食分量，避免睡前进食，饱腹后及时停止进食，同时杜绝餐后立即平躺、剧烈活动等行为。

在饮食结构上，建议患者选择易消化、低脂、高膳食纤维的食物。同时需重视科学补水，补水对出现腹泻或便秘症状的患者尤为关键，多数用药患者存在进食、饮水偏少的问题，规律足量饮水是干预不良反应的重要环节。饮水时需小口饮用、避免使用吸管，防止大量空气进入消化系统，加重胃肠道不适。

此外，出现恶心、呕吐、腹泻症状的患者，需严格规避乳制品、人工甜味剂饮品、等渗饮料及碳酸饮料，同时忌食辛辣刺激食物、调味品及罐装加工食品，最大程度降低饮食因素对胃肠道的刺激。

缓慢加量是处方用药的核心原则，快速提升剂量会显著增加胃肠道不良反应风险。临床需从最低推荐剂量起始，该方案对体质敏感人群、老年患者及合并基础胃肠疾病的患者尤为重要。若用药后出现胃肠不适，应暂停上调剂量，可维持当前剂量并将调整周期延长2~4周，待症状完全消退后，再从既往耐受的剂量重新缓慢加量。针对长期耐受不佳的患者，可选用低于最大推荐剂量的方案维持治疗；也可暂时停药，待不良反应消失后重启治疗。

Hepatology Digest: In current clinical practice, what medication-related pitfalls do physicians commonly fall into? How do you believe the overall diagnosis and treatment outcomes for MASLD should be optimized?

Prof. Sanja Klobucar：The new generation of incretin-based drugs, represented by semaglutide and tirzepatide, has thoroughly transformed the clinical management of obesity. These agents can achieve weight loss effects comparable to those previously only attainable with bariatric surgery. In addition, they deliver multiple health benefits and markedly improve patients' quality of life.

However, the efficacy of these drugs is highly dependent on sustained medication use. Premature discontinuation will greatly compromise their therapeutic value. Current clinical data show that more than half of patients stop treatment within the first year, and adverse drug reactions are the leading cause of early treatment withdrawal. Therefore, developing scientific strategies for the prevention and management of adverse reactions is critical to ensuring satisfactory treatment outcomes.

To address this issue, clinicians can adopt a simple and practical 3Es management framework, namely Educate and Explain, Eat Differently, and Escalate Slowly. Before initiating pharmacotherapy, clinicians should provide thorough patient education, including detailed instructions on drug administration, treatment expectations, potential adverse reactions and corresponding countermeasures. It is also important to inform patients that most adverse reactions to these drugs are mild to moderate and transient, and can be effectively managed, so as to relieve their concerns.

The predominant adverse reactions of these drugs are gastrointestinal symptoms, including nausea, vomiting, diarrhea and constipation. Patients can relieve such discomfort by adjusting their dietary habits and food choices. In terms of eating habits, patients are advised to chew food thoroughly, take smaller and more frequent meals, and control food portions. They should avoid eating right before bedtime and stop eating once full. Meanwhile, lying down or engaging in strenuous exercise immediately after meals should also be avoided.

As for dietary composition, patients are recommended to choose easily digestible, low-fat and high-fiber foods. Adequate water intake should also be emphasized, which is especially vital for patients suffering from diarrhea or constipation. In fact, many patients on these medications tend to eat and drink insufficiently, and regular and adequate water intake is an important measure to mitigate adverse reactions. Patients should sip water slowly and avoid using straws, as excessive air entering the digestive tract will worsen gastrointestinal discomfort.

Furthermore, patients with nausea, vomiting or diarrhea must strictly avoid dairy products, artificially sweetened beverages, isotonic drinks and carbonated drinks. Spicy and irritating foods, condiments, as well as canned and processed foods should also be excluded from their diet. These measures can minimize gastrointestinal irritation caused by diet and ensure the smooth progress of treatment.

A key prescribing principle is to start low and go slow, as rapid dose escalation significantly increases the risk of GI adverse effects. Treatment should begin at the lowest recommended dose, with patients carefully following dosing instructions. This approach is especially important for sensitive individuals, older adults, and patients with pre-existing GI conditions. If GI symptoms occur, dose escalation should be delayed until symptoms resolve, the titration phase may be extended by 2–4 weeks at the current dose, and patients may need to return temporarily to the previous tolerated dose before attempting a more gradual increase. For persistent tolerability issues, a lower maintenance dose than the maximum recommended may be appropriate, and treatment can be temporarily interrupted and resumed once adverse effects have resolved.

（来源：《国际肝病》编辑部）

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