What are the recommendations for using terizepitide in the Surmount trial for adults or geriatric individuals?

Tirzepatide (Surmount Trial) for Weight Management

Primary Recommendation

Tirzepatide at maximum tolerated doses (10 mg or 15 mg weekly) should be used for adults with obesity (BMI ≥30) or overweight with weight-related complications (BMI ≥27), as it produces substantial weight reduction of 15-20% at 3 years and reduces progression to type 2 diabetes by 88-93%. 1, 2

Evidence from SURMOUNT Trials

Weight Loss Efficacy

• At 176 weeks (3.5 years), tirzepatide produced mean weight reductions of:

  • 5 mg dose: -12.3%
  • 10 mg dose: -18.7%
  • 15 mg dose: -19.7%
  • Placebo: -1.3% 2

• At medium-term (12-18 months), tirzepatide resulted in -16.03% mean weight reduction versus placebo 3

• Clinically significant weight loss (≥5%) was achieved 3.6 times more frequently with tirzepatide versus placebo 3

Diabetes Prevention

• Progression to type 2 diabetes was reduced by 93% during the 176-week treatment period (1.3% vs 13.3% with placebo; HR 0.07) 2

• After 17 weeks off treatment, diabetes risk remained 88% lower (2.4% vs 13.7%; HR 0.12), demonstrating sustained benefit 2

Cardiovascular and Metabolic Benefits

• Major adverse cardiovascular events (MACE) showed no significant difference but trended toward benefit (RR 0.75 at medium-term, RR 0.56 at long-term) 3

• In obstructive sleep apnea patients, tirzepatide reduced apnea-hypopnea index by 20-24 events/hour, improved hypoxic burden, reduced hsCRP, and lowered systolic blood pressure 4

Dosing Protocol

Start at 2.5 mg weekly for 4 weeks, then escalate:

• Increase to 5 mg weekly for ≥4 weeks
• Increase to 10 mg weekly for ≥4 weeks
• Target maximum tolerated dose of 15 mg weekly 1, 2

The 15 mg dose is the preferred target as it produces superior efficacy compared to lower doses 5, 2

Safety Profile

Common Adverse Events

• Gastrointestinal effects (nausea, vomiting, diarrhea) are most common, typically mild-to-moderate, and occur primarily during dose escalation in the first 20 weeks 2, 4

• Non-serious adverse events increased with tirzepatide (RR 1.33 at medium-term, RR 1.05 at long-term) 3

Serious Adverse Events

• Serious adverse events showed no significant difference from placebo (RR 0.99 at medium-term, RR 1.14 at long-term), though certainty of evidence is very low 3

• Mortality showed no significant difference (RR 0.79 at medium-term, RR 0.83 at long-term) 3

• Discontinuation due to adverse events may be increased (RR 2.06 at medium-term, RR 1.64 at long-term), though evidence certainty is low 3

Special Populations

Geriatric Patients

Tirzepatide can be used in adults up to age 70 years based on trial enrollment, but no high-quality data exist for older adults 5

• Pivotal trials enrolled participants up to age 70 years 5
• For patients >70 years, apply general principles for elderly medication management: monitor for volume depletion, orthostatic hypotension, and gastrointestinal tolerance 5
• SGLT2 inhibitor principles (a related class) suggest caution in frail elderly or those prone to orthostasis 5

Patients with Cardiovascular Disease

Avoid tirzepatide in patients with uncontrolled cardiovascular disease until more outcome data are available 5

• No large cardiovascular outcome trials exist yet for tirzepatide, though SURMOUNT-MMO is ongoing 1
• Current data show no increased cardiovascular risk and potential benefit 3, 4

Patients with Prediabetes

Tirzepatide is particularly indicated for patients with obesity and prediabetes given the dramatic 93% reduction in diabetes progression 2

Patients with Obstructive Sleep Apnea

Tirzepatide effectively treats moderate-to-severe OSA in patients with obesity, reducing AHI by 20-24 events/hour whether or not patients use PAP therapy 4

Quality of Life Outcomes

Tirzepatide produces clinically meaningful improvements in quality of life, particularly in:

• Physical function (IWQOL-Lite-CT physical function domain: MD 9.91) 3
• Weight-related psychological and social functioning 6
• Greater improvements occur in patients achieving higher weight loss thresholds (≥15%, ≥20%, ≥25%) 6
• Patients with baseline physical limitations experience greater QOL improvements than those without limitations 6

Monitoring Requirements

During Treatment

• Weight and metabolic parameters at each visit
• Blood glucose monitoring in patients with prediabetes to detect diabetes progression
• Cardiovascular assessment including blood pressure monitoring 4
• Gastrointestinal tolerance especially during dose escalation 2

Long-term Surveillance

• Continue treatment indefinitely as weight regain occurs after discontinuation (similar to other chronic disease management) 2
• Annual diabetes screening in patients with prediabetes, as some progression may occur even with treatment 2

Contraindications and Precautions

Absolute contraindications:

• Personal or family history of medullary thyroid carcinoma
• Multiple endocrine neoplasia syndrome type 2
• Pregnancy (teratogenic risk similar to other GLP-1 agonists) 5

Relative contraindications:

• History of pancreatitis
• Severe gastrointestinal disease
• Uncontrolled cardiovascular disease 5

Clinical Context

All SURMOUNT trials were funded by Eli Lilly, raising concerns about potential conflicts of interest 3, 2

The evidence base is strongest for:

• Adults aged 36-70 years
• Patients from middle- and high-income countries
• Patients with obesity-related comorbidities (diabetes, prediabetes, OSA, cardiovascular risk factors) 1, 3, 2

Further independent studies are needed in underrepresented populations and for patients >70 years 3