When should tirzepatide (a dual GIP (glucose-dependent insulinotropic polypeptide) and GLP-1 (glucagon-like peptide-1) receptor agonist) be considered for patients with type 2 diabetes or obesity, particularly those with inadequate glycemic control or significant weight-related comorbidities?

Screening for Tirzepatide Use

Primary Indications

Tirzepatide should be considered for patients with type 2 diabetes who have inadequate glycemic control (A1C >7% on current therapy) and/or obesity (BMI ≥30 kg/m²), particularly when weight loss is a priority treatment goal. 1, 2

For Type 2 Diabetes Management

• Initiate tirzepatide when patients fail to achieve individualized glycemic targets despite metformin and/or SGLT2 inhibitor therapy, as it demonstrates superior A1C reduction (1.87-2.59%) compared to other glucose-lowering medications 1, 3, 4
• Prioritize tirzepatide over standard GLP-1 receptor agonists when maximum weight loss is needed, as it achieves 20.9% weight reduction versus 14.9% with semaglutide 2.4mg 2, 5
• Consider tirzepatide for patients with metabolic dysfunction-associated steatotic liver disease (MASLD) or MASH, as dual GIP/GLP-1 agonists show beneficial effects on liver fibrosis 1
• Use tirzepatide in patients with advanced CKD (eGFR <30 mL/min/1.73 m²) as GLP-1 receptor agonists are preferred for glycemic management with lower hypoglycemia risk 1

For Obesity Management (Without Diabetes)

• Prescribe tirzepatide for adults with BMI ≥30 kg/m² without additional requirements 2
• Prescribe tirzepatide for adults with BMI ≥27 kg/m² plus at least one weight-related comorbidity (hypertension, dyslipidemia, obstructive sleep apnea, cardiovascular disease) 2
• Prioritize tirzepatide over semaglutide when maximum weight loss is the primary goal, achieving mean weight loss of 20.9% at 72 weeks with the 15mg dose 2, 5

Pre-Treatment Screening Requirements

Absolute Contraindications to Identify

• Screen for personal or family history of medullary thyroid cancer or multiple endocrine neoplasia syndrome type 2 - this is an absolute contraindication 1, 2
• Assess for current pregnancy or planned pregnancy - tirzepatide is not recommended during pregnancy 2

Baseline Laboratory Testing

• Obtain A1C and fasting glucose to establish baseline glycemic control 1
• Check comprehensive metabolic panel including renal function (eGFR) and liver enzymes 1
• Measure lipid panel (total cholesterol, LDL, HDL, triglycerides) to assess cardiovascular risk 2
• Consider thyroid function testing if clinically indicated, though not routinely required 2

Clinical History Assessment

• Document history of pancreatitis - use with caution if present, though causality not definitively established 1, 2
• Assess for severe gastroparesis or GI motility disorders - tirzepatide may worsen symptoms due to delayed gastric emptying 2
• Review all current medications to identify weight-promoting drugs and consider alternatives 2
• Document failed lifestyle modifications (diet and exercise attempts) for insurance authorization 2

Cardiovascular Risk Stratification

• Identify patients with established cardiovascular disease - while tirzepatide shows cardiovascular benefits, semaglutide 2.4mg has proven cardiovascular outcome data (20% reduction in MACE) 2
• Assess blood pressure as baseline, since weight loss will likely require antihypertensive medication adjustment 2

Special Population Considerations

Patients on Insulin or Insulin Secretagogues

• Plan to reduce basal insulin by 20% when initiating tirzepatide to prevent hypoglycemia 2
• Consider discontinuing or reducing sulfonylureas due to increased hypoglycemia risk when combined with tirzepatide 1
• Strongly consider discontinuing prandial insulin entirely or reduce by 50% at tirzepatide initiation 2

Patients on Other Incretin-Based Therapies

• Discontinue DPP-4 inhibitors before starting tirzepatide - concurrent use is not recommended due to lack of additional benefit 1
• Do not combine tirzepatide with other GLP-1 receptor agonists - this is pharmacologically redundant and potentially harmful 2

Women of Reproductive Age

• Advise women using oral contraceptives to switch to non-oral methods or add barrier contraception for 4 weeks after initiation and each dose escalation 2

When NOT to Initiate Tirzepatide

• Avoid in patients with A1C >10% or blood glucose ≥300 mg/dL with symptoms of hyperglycemia - insulin should be initiated first 1
• Do not use in patients with evidence of significant insulin deficiency - GLP-1 receptor agonists are preferred only when insulin deficiency is absent 1
• Defer in patients with recent heart failure decompensation due to potential increased risk of exacerbation 2

Perioperative Considerations

• For elective surgery, discontinue tirzepatide at least 3 weeks (three half-lives) before the procedure to minimize delayed gastric emptying and aspiration risk 2
• Consider gastric ultrasound pre-operatively to assess residual gastric contents in patients on tirzepatide 2

Common Pitfalls to Avoid

• Do not wait for treatment failure on multiple oral agents before considering tirzepatide - early initiation in appropriate candidates leads to better outcomes 1
• Do not prescribe tirzepatide without documenting lifestyle modification attempts - this is required for insurance authorization and clinical appropriateness 2
• Do not overlook the need for lifelong treatment - patients must understand that discontinuation results in regain of 50-67% of lost weight within one year 2, 5
• Do not ignore the cost barrier - tirzepatide costs approximately $1,272-$1,283 per 30-day supply, requiring financial planning and insurance verification 2