SEMAGLUTIDE INJ,SOLN
Clinical Criteria Summary
Document 328: Semaglutide 2mg OZEMPIC Guidance July 2024
Indication & Patient Population
- Type 2 diabetes
- Patients currently treated with semaglutide 1mg requiring additional glycemic control
- Trial population demographics: mean age 58 years, 59% men, 88% white, mean duration of diabetes 9.5 years, mean A1C 8.9%, mean fasting plasma glucose 194 mg/dL, mean weight 99.3 kg, 53% on sulfonylureas
Efficacy & Glycemic Control
- Indicated as add-on to metformin +/- sulfonylureas
- Primary outcome: Change from baseline at week 40 in A1C (estimated treatment difference between 2mg and 1mg was 0.2%)
- A1C <7% achieved in 64% of patients on 2mg vs 56% on 1mg
- Fasting plasma glucose change: -59 mg/dL for 2mg vs -55 mg/dL for 1mg
- Blood pressure changes at week 40: -5.3 mmHg systolic and -0.8 mmHg diastolic for 2mg; -4.5 mmHg systolic and -0.4 mmHg diastolic for 1mg
Weight Management
- Change in body weight at week 40: -6.4 kg for 2mg vs -5.6 kg for 1mg (estimated treatment difference -0.77 kg)
- Percentage of patients with weight loss: 7.2% for 2mg vs 6.2% for 1mg
Safety & Adverse Events
- Gastrointestinal adverse events (nausea, vomiting, diarrhea) and hypoglycemia were comparable between doses
- No increase in other adverse events of interest with the 2mg dose compared to the 1mg dose: diabetic retinopathy complications, hepatobiliary issues, acute gallstone disease, pancreatitis, cardiovascular disease, allergic reactions
Intensification & Clinical Considerations
- Verify adherence to current therapy
- Optimize current non-GLP1 agonist anti-glycemic medications as appropriate
- Consider addition of empagliflozin or insulin if appropriate
Formulary/Availability
- Available on VANF; doses up to 1 mg are on National Contract (2mg dose is not on National Contract)
Document 223: Semaglutide OZEMPIC Criteria in Type 2 Diabetes April 2026
Indication & Inclusion Criteria
- Diagnosis of Type 2 diabetes mellitus (T2DM)
- Must meet ONE of the following additional criteria:
- Patient has established ASCVD and/or CKD and is not a good candidate for empagliflozin
- Patient whose glycemic goals are not met with empagliflozin plus maximally tolerated doses of metformin, unless unable to use
- To replace selected drugs (insulin, sulfonylurea, DPP-4, TZD), irrespective of A1c, with intent to reduce weight, hypoglycemic risk or improve outcomes
Exclusion Criteria & Contraindications
- Personal or family history of medullary thyroid carcinoma or Multiple Endocrine Neoplasia syndrome type 2 (contraindication/boxed warning against use)
- Severe gastrointestinal dysmotility including gastroparesis (unless risks/benefits are discussed with the patient and documented in the Federal EHR with a plan to monitor and follow GI symptoms)
- History of pancreatitis (does not pertain to patients for whom the cause of pancreatitis is known and no longer presents a risk)
- Pregnancy (Insulin is generally preferred; discontinue semaglutide at least 2 months before a planned pregnancy due to long washout period; use only if potential benefit justifies potential risk to fetus/mother; registry enrollment recommended)
- Known PDR, severe NPDR, clinically significant ME, or DME (unless risks/benefits are discussed with the patient and documented in the Federal EHR with a plan to monitor and follow-up with an eye specialist who is informed upon initiation)
- Low body weight and/or presence of sarcopenia (unless risks/benefits are discussed with the patient and documented in the Federal EHR with a plan to closely monitor and follow changes in weight)
- Concomitant use of DPP-4 inhibitors (additional benefit has not been shown)
Comorbidities & Special Populations
- ASCVD: Defined as history of acute coronary syndrome or myocardial infarction, stable or unstable angina, coronary heart disease with/without revascularization, other arterial revascularization, stroke, or atherosclerotic peripheral artery disease
- CKD: Defined as eGFR <60mL/min/1.73m2 OR Urinary Albumin-to-Creatinine Ratio >= 30mg/g
- Type 1 Diabetes: Not FDA approved for glycemic control; small retrospective studies show improvements in body weight and glycemic measures when added to insulin; ongoing studies investigating efficacy/safety; refer to weight management CFU for patient selection guidance
- MASLD: Refers to liver steatosis with metabolic risk factors (obesity, T2DM, hypertension, dyslipidemia); can progress to MASH; reversible with weight loss, alcohol avoidance, and management of metabolic risk factors; refer to weight management and MASH CFU for guidance
- Breastfeeding: No data on presence in human milk or effects on infant/milk production; consider developmental/health benefits of breastfeeding alongside clinical need and potential adverse effects
- Pancreatitis Risk Factors: hypertriglyceridemia (>1000 mg/dL), gallstones with intact gallbladder, alcohol use disorder/excessive use
Monitoring & Clinical Management Requirements
- Diabetic eye examination results completed within the past 12 months must be on file before considering a GLP-1 agonist
- Patients with a history of diabetic retinopathy require planned follow-up with an eye provider to monitor for progression
- Ophthalmology consult required if concerns arise regarding use in patients with diabetic retinopathy
- Insulin may be considered prior to GLP-1 agonist; preferred if patient is symptomatic, blood sugars >300 mg, A1c >10%, or desired A1C reduction exceeds GLP-1 capability
- Metformin should be used prior to adding semaglutide/another GLP-1RA unless unable to use (contraindicated at eGFR <30 mL/min/1.73 m2)
- Oral semaglutide (nonformulary) reserved for patients physically unable to use injectable therapy (e.g., dexterity or vision limitations)
Additional Prescribing & Formulary Notes
- Semaglutide and empagliflozin reduce MACE, slow CKD progression, and lead to weight loss; semaglutide improves symptoms in HFpEF and reduces stroke risk
- Direct evidence from prospective RCTs is lacking to confirm that combining semaglutide + empagliflozin further reduces CV risk or slows CKD progression vs. either agent alone
- Empagliflozin risks include volume depletion, genitourinary tract infections, genital mycotic infections, ketoacidosis; not recommended for glycemic control if eGFR <30 or for CV/CKD risk reduction initiation if eGFR <20
- GLP-1RA combination with alpha glucosidase inhibitors or meglitinides is not recommended due to lack/insufficient data
- Refer to VA/DoD Type 2 Diabetes Guidelines for individualizing A1c targets
Document 919: Weight Management Medication FAQ Sep 2026
Criteria for Chronic Weight Management Medications (BUPROPION/NALTREXONE TAB,SA; LIRAGLUTIDE INJ,SOLN; ORLISTAT CAP,ORAL; PHENTERMINE/TOPIRAMATE CAP,SA; SEMAGLUTIDE INJ,SOLN; SEMAGLUTIDE TAB; TIRZEPATIDE INJ,SOLN; TIRZEPATIDE INJECTION; TIRZEPATIDE PEN INJECTOR)
- Prescribing Authority and Clinical Practice Setting
- May be prescribed by any credentialed provider with no restrictions on provider type or clinical practice location.
- Facilities are not permitted to impose local restrictions on who may prescribe these medications or in what setting prescribing must occur.
- Comprehensive Lifestyle Intervention (CLI) Participation Requirements
- All inclusion criteria require verifiable participation in a CLI targeting behavioral, dietary, and physical activity components.
- Eligibility requires documentation of CLI participation within the past year on at least one occasion as part of a course of intervention.
- Medications may be initiated at any time during active CLI participation or contemporaneously based on provider-patient shared decision making.
- Ongoing CLI Participation and Treatment Monitoring
- Patients should ideally continue to actively participate in an ongoing CLI tailored to individual needs.
- Medications must be monitored and discontinued if initial weight loss goals (per prescribing information) are not achieved.
- Patients achieving long-term weight loss goals should receive ongoing support and periodic reassessment of their treatment plan as clinically indicated.
- Local Policy Modification and Clinical Context
- National CFU cannot be modified at the local or VISN level.
- Clinicians must use this guidance and interpret it in the clinical context of the individual patient.
- Individual cases that are exceptions to exclusion and inclusion criteria should be adjudicated at the local facility according to P&T committee and pharmacy services policy and procedures.