How should I manage an obese adult on tirzepatide (Mounjaro) 2.5 mg weekly who is not losing weight, has work‑related stress, hyperkeratotic xerosis on palms and soles, hypertension 155/100 mmHg with tachycardia 105 bpm, regular bowel movements and nocturia 1‑2 times nightly?

Management of Obese Adult on Tirzepatide 2.5 mg with Inadequate Weight Loss, Hypertension, and Metabolic Concerns

Immediate Priority: Optimize Tirzepatide Dosing

You must escalate tirzepatide immediately—the 2.5 mg dose is only for initial tolerability assessment, not therapeutic weight loss. The patient has completed four doses (approximately 4 weeks), which meets the minimum duration before escalation. 1, 2

Tirzepatide Dose Escalation Protocol

• Week 5–8: Increase to 5 mg weekly (the first therapeutic dose), which produces HbA1c reductions of 1.9–2.1% and weight loss of approximately 5.5 kg. 1
• Week 9–12: Escalate to 10 mg weekly after 4 weeks on 5 mg if gastrointestinal tolerance is acceptable. 1
• Week 13+: Consider 15 mg weekly (maximum dose) after an additional 4 weeks if further weight loss is needed; the 15 mg dose achieves 20.9% weight reduction at 72 weeks. 3, 1, 2

Critical timing: Do not assess weight-loss efficacy until 12–16 weeks on a therapeutic dose (5 mg or higher). 1, 2 The current lack of weight loss at 2.5 mg is expected and does not indicate treatment failure. 1

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Hypertension Management: Dual Approach

Your patient's BP of 155/100 mmHg with tachycardia (105 bpm) requires immediate pharmacologic intervention while tirzepatide is optimized.

Initiate Antihypertensive Therapy Now

• Start a beta-blocker (e.g., metoprolol 25–50 mg daily) to address both hypertension and tachycardia (105 bpm). Beta-blockers are particularly appropriate given the elevated heart rate and potential for GLP-1/GIP agonist-related tachycardia. 2, 4
• Add an ACE inhibitor or ARB (e.g., lisinopril 10 mg daily) if beta-blocker monotherapy is insufficient after 2–4 weeks. 5

Expected Blood Pressure Benefits from Tirzepatide

• Tirzepatide produces a net reduction of 6.8 mmHg systolic and 4.2 mmHg diastolic BP by 72 weeks, with the most rapid decline occurring in the first 24 weeks. 5
• Weight loss explains approximately 68% of systolic and 71% of diastolic BP reduction with tirzepatide. 5
• Monitor BP every 2–4 weeks during dose escalation; antihypertensive medications may require downward adjustment as weight loss progresses. 1, 5

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Nocturia Evaluation and Management

Nocturia 1–2 times nightly in an obese patient warrants screening for obstructive sleep apnea (OSA) and diabetes.

Immediate Screening

• Obtain HbA1c and fasting glucose to exclude prediabetes (HbA1c 5.7–6.4%) or type 2 diabetes (HbA1c ≥6.5%). 1
• Screen for OSA using the STOP-BANG questionnaire; if positive, refer for polysomnography. Tirzepatide improves OSA severity in addition to weight loss. 6
• Check urinalysis to exclude urinary tract infection or glucosuria. 1

Tirzepatide's Impact on Nocturia

• If nocturia is secondary to OSA or diabetes, tirzepatide will likely improve symptoms as weight loss progresses and metabolic parameters normalize. 6
• Reassess nocturia at 12–16 weeks after reaching therapeutic tirzepatide doses. 1

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Hyperkeratotic Xerosis (Palms and Soles): Dermatologic Evaluation

Dry, cracked, thickened skin on palms and soles requires exclusion of underlying metabolic or dermatologic conditions.

Differential Diagnosis and Workup

• Screen for hypothyroidism (TSH, free T4) and vitamin deficiencies (vitamin D, B12, folate), as these are common in obesity and can cause skin changes. 1
• Evaluate for psoriasis or eczema with dermatology referral if skin changes persist despite moisturization. 1
• Assess for diabetes-related complications (e.g., diabetic dermopathy) once HbA1c results are available. 1

Symptomatic Management

• Prescribe a high-potency emollient (e.g., urea 40% cream) for palms and soles twice daily. 1
• Optimize vitamin D supplementation if deficient, as deficiency impairs weight-loss efficacy and may contribute to skin changes. 1

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Work-Related Stress: Behavioral and Lifestyle Optimization

Stress management is critical for weight-loss success, as chronic stress impairs adherence to lifestyle modifications and may worsen metabolic parameters.

Structured Interventions

• Refer to a registered dietitian for a 500-kcal daily deficit meal plan tailored to the patient's schedule and preferences. 3, 1
• Prescribe ≥150 minutes per week of moderate-intensity physical activity (e.g., brisk walking), with resistance training to preserve lean body mass. 3, 1
• Recommend behavioral counseling or cognitive-behavioral therapy (CBT) to address stress-related eating and improve medication adherence. 3, 1

Monitoring Adherence

• Track weight monthly to ensure continued efficacy of tirzepatide and lifestyle modifications. 2
• Assess medication adherence at every visit; missed doses reduce efficacy. 1

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Monitoring Schedule and Follow-Up

Week 4 (Current Visit)

• Escalate tirzepatide to 5 mg weekly. 1
• Initiate beta-blocker (e.g., metoprolol 25–50 mg daily) for hypertension and tachycardia. 2, 4
• Order HbA1c, fasting glucose, TSH, vitamin D, lipid panel, and urinalysis. 1
• Refer to dietitian and behavioral counseling. 3, 1

Week 8

• Escalate tirzepatide to 10 mg weekly if GI tolerance is acceptable. 1
• Reassess BP and heart rate; adjust antihypertensives as needed. 5
• Review laboratory results and address any abnormalities (e.g., vitamin D supplementation if deficient). 1

Week 12–16

• Evaluate weight loss (goal: ≥5% body weight reduction from baseline). 1, 2
• Reassess nocturia, skin changes, and stress management. 1
• Consider escalation to 15 mg weekly if weight loss is <5% or additional weight loss is needed. 1, 2

Every 3 Months Thereafter

• Monitor weight, BP, HbA1c (if diabetic/prediabetic), and cardiovascular risk factors. 1
• Adjust antihypertensives as weight loss progresses. 5

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Common Pitfalls to Avoid

• Do not wait to escalate tirzepatide beyond 4 weeks on 2.5 mg—this dose is not therapeutic. 1
• Do not assess weight-loss efficacy before 12–16 weeks on a therapeutic dose (5 mg or higher). 1, 2
• Do not ignore hypertension while waiting for tirzepatide to take effect—initiate antihypertensives immediately. 5
• Do not overlook OSA or diabetes as causes of nocturia—screen early. 1, 6
• Do not assume skin changes are benign—rule out metabolic and dermatologic conditions. 1

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Expected Outcomes with Optimized Therapy

• Weight loss: 15–20.9% body weight reduction at 72 weeks with tirzepatide 10–15 mg. 3, 1, 2
• Blood pressure: 6.8/4.2 mmHg reduction by 72 weeks, with most improvement in the first 24 weeks. 5
• Nocturia: Likely improvement if secondary to OSA or diabetes. 6
• Skin changes: Resolution with treatment of underlying metabolic abnormalities and topical therapy. 1