Trulicity
Indications
Dulaglutide is FDA-approved for type 2 diabetes glycemic control in adults and pediatric patients aged 10 years and older, and for cardiovascular risk reduction in adults with type 2 diabetes who have established cardiovascular disease or multiple cardiovascular risk factors. The cardiovascular indication followed the REWIND trial, which uniquely enrolled a population in which 69% had no prior cardiovascular event, demonstrating MACE reduction in primary prevention as well as secondary prevention contexts.
| Indication | Approved Population | Therapy Type | Status |
|---|---|---|---|
| Type 2 diabetes — glycemic control | Adults (≥18 years) | Adjunct to diet and exercise; mono- or combination | FDA Approved |
| Type 2 diabetes — glycemic control | Pediatric ≥10 years | Adjunct to diet and exercise; mono- or combination | FDA Approved |
| Reduction of MACE (CV death, non-fatal MI, non-fatal stroke) | Adults with T2DM and established CVD or multiple CV risk factors | Adjunctive (1.5 mg dose specifically studied) | FDA Approved |
| Adjunctive weight management in T2DM with overweight/obesity | Adults | Adjunctive | Off-Label |
| Metabolic-associated steatotic liver disease (MASLD/MASH) in T2DM | Adults with T2DM | Adjunctive | Off-Label |
Dulaglutide is not indicated for type 1 diabetes or diabetic ketoacidosis. It has not been formally evaluated for chronic weight management in patients without diabetes; semaglutide and tirzepatide hold FDA approvals within the GLP-1/GIP class for that indication.
Adjunctive weight management in T2DM (Evidence: Moderate) — In AWARD-11, mean weight reductions at 36 weeks were 3.1 kg (1.5 mg), 4.0 kg (3 mg), and 4.7 kg (4.5 mg). Magnitude is smaller than with semaglutide 2.4 mg or tirzepatide; reasonable when a once-weekly GLP-1 RA is otherwise appropriate.
MASLD / MASH in T2DM (Evidence: Low) — Mechanistic and small-trial data suggest improvement in hepatic enzymes and steatosis surrogates, but no histological-endpoint trials of dulaglutide. ADA 2026 Standards of Care prefer semaglutide and tirzepatide where MASH is the priority.
CV risk reduction in adults without diabetes (Evidence: Very Low) — REWIND enrolled only adults with T2DM; class-level evidence in non-diabetics (e.g., SELECT for semaglutide) cannot be extrapolated to dulaglutide.
Dosing
Dulaglutide is administered subcutaneously once weekly, on the same day each week, in the abdomen, thigh, or upper arm. Administration is independent of meals. A single-dose prefilled pen delivers a fixed dose; partial administration is not possible. Initiate at the lowest dose to mitigate gastrointestinal adverse effects, then escalate based on glycemic response and tolerability after at least 4 weeks at each dose level.
| Clinical Scenario | Starting Dose | Maintenance Dose | Maximum Dose | Notes |
|---|---|---|---|---|
| T2DM — adult, glycemic control | 0.75 mg SC weekly | 1.5 mg SC weekly | 4.5 mg SC weekly | Increase by 1.5 mg increments after ≥4 weeks if HbA1c not at goal. Step sequence: 0.75 → 1.5 → 3 → 4.5 mg. Most patients achieve target on 1.5 mg. |
| T2DM with established CVD or risk factors | 0.75 mg SC weekly | 1.5 mg SC weekly | 1.5 mg SC weekly | REWIND demonstrated MACE reduction at 1.5 mg specifically. Higher doses lack dedicated CV outcomes data. Escalate beyond 1.5 mg only if added glycemic control is needed. |
| T2DM — inadequate control on 1.5 mg | 3 mg SC weekly | 3 mg SC weekly | 4.5 mg SC weekly | Escalate to 4.5 mg after ≥4 weeks at 3 mg if HbA1c not at goal. AWARD-11: 4.5 mg gave additional 0.24% HbA1c and 1.6 kg weight reduction vs 1.5 mg at 36 wk. |
| Pediatric T2DM (≥10 years) | 0.75 mg SC weekly | 0.75–1.5 mg SC weekly | 1.5 mg SC weekly | Increase to 1.5 mg after ≥4 weeks if needed. AWARD-PEDS showed HbA1c benefit but no significant change in BMI. 3 and 4.5 mg doses not approved for pediatric use. |
| Renal impairment (any stage, including ESRD) | 0.75 mg SC weekly | 1.5 mg SC weekly | 4.5 mg SC weekly | No dose adjustment per FDA PI. Use with caution in ESRD; monitor renal function if severe GI symptoms occur. |
| Hepatic impairment | 0.75 mg SC weekly | 1.5 mg SC weekly | 4.5 mg SC weekly | No PK-based adjustment required. Limited clinical experience in moderate-to-severe impairment. |
| Concurrent insulin or sulfonylurea | 0.75 mg SC weekly | 1.5 mg SC weekly | 4.5 mg SC weekly | Reduce concomitant insulin or sulfonylurea dose at initiation to mitigate hypoglycemia. Stopping the SU is often appropriate as glycemia improves. |
If a dose is missed and at least 3 days (72 hours) remain until the next scheduled dose, administer it as soon as possible and resume the regular schedule. If less than 3 days remain, skip the missed dose entirely and resume on the regular day. The day of weekly administration may be changed as long as at least 3 days have elapsed since the last dose — useful when aligning the injection day with a clinic visit or travel.
The 2023 ASA consensus and 2024 multi-society guidance suggest holding weekly GLP-1 receptor agonists for one week prior to elective procedures requiring general anesthesia or deep sedation, due to delayed gastric emptying and aspiration risk. Decisions should be individualized through shared decision-making, balancing aspiration risk against glycemic instability. The November 2024 FDA label update added a warning about pulmonary aspiration during anesthesia or deep sedation but acknowledges that data are insufficient to mandate a specific hold duration.
Pharmacology
Mechanism of Action
Dulaglutide is a long-acting glucagon-like peptide-1 (GLP-1) receptor agonist constructed by linking two modified GLP-1 analogue chains to a human IgG4 Fc fragment. Activation of GLP-1 receptors on pancreatic beta cells potentiates glucose-dependent insulin secretion — insulin release rises only when serum glucose is elevated, conferring a low intrinsic hypoglycemia risk during monotherapy. Simultaneously, dulaglutide suppresses inappropriately elevated post-prandial glucagon release from alpha cells, slows gastric emptying to blunt post-meal glucose excursions, and acts on hypothalamic appetite circuits to reduce caloric intake and body weight.
The IgG4 Fc fusion is the structural feature that differentiates dulaglutide from shorter-acting incretins. It confers resistance to dipeptidyl peptidase-4 (DPP-4) and reduces renal clearance, extending the half-life sufficiently to support once-weekly subcutaneous dosing. The cardiovascular benefit observed in REWIND — a 12% relative reduction in the primary MACE composite (HR 0.88, 95% CI 0.79–0.99) — appears to extend beyond glucose lowering, with proposed mechanisms including modest blood pressure reduction, weight loss, and anti-inflammatory effects on the vasculature.
ADME Profile
| Parameter | Value | Clinical Implication |
|---|---|---|
| Absorption | Bioavailability ~65% (0.75 mg) and ~47% (1.5 mg) SC; Tmax ~48 h | Slow, sustained absorption supports weekly dosing. Injection site (abdomen, thigh, upper arm) does not meaningfully alter exposure. |
| Distribution | Vd ~19.2 L (0.75 mg) and ~17.4 L (1.5 mg); largely confined to plasma | Minimal tissue penetration. Not subject to plasma-protein-binding-mediated drug interactions. |
| Metabolism | Catabolized into amino acids via general protein degradation pathways | No CYP450 involvement → minimal pharmacokinetic interactions with most small-molecule drugs. |
| Elimination | Catabolic clearance; t½ ~5 days; steady state in 2–4 weeks | No dose adjustment required for renal or hepatic impairment. Pharmacologic effect persists for several weeks after discontinuation. |
Side Effects
The adverse-effect profile is dominated by gastrointestinal symptoms, which are dose-related and most pronounced during the first 4 weeks after initiation or each dose escalation. Frequencies below reflect the FDA-approved labeling: pooled placebo-controlled trial data for the 0.75 mg and 1.5 mg doses (N=1670 dulaglutide; mean exposure 23.8 weeks) and the AWARD-11 dose-ranging trial for the 3 mg and 4.5 mg doses (N=1842).
| Adverse Effect | Incidence (Placebo) | Clinical Note |
|---|---|---|
| Nausea | 21.1% (5.3%) | Dose-related; typically peaks within 2–4 weeks of initiation or escalation, then declines. |
| Vomiting | 12.7% (2.3%) | Higher with 1.5 mg vs 0.75 mg (6.0%). Persistent vomiting → hold and reassess hydration. |
| Diarrhea | 12.6% (6.7%) | Often transient. May worsen briefly with each dose-escalation step. |
| Adverse Effect | Incidence (Placebo) | Clinical Note |
|---|---|---|
| Abdominal pain | 9.4% (4.9%) | Usually mild–moderate. Severe or persistent pain → exclude pancreatitis (lipase, imaging). |
| Decreased appetite | 8.6% (1.6%) | Often welcomed; monitor for unintended weight loss in older or frail patients. |
| Dyspepsia | 5.8% (2.3%) | Smaller, slower meals reduce symptoms. |
| Sinus tachycardia | 5.6% (3.0%) | Mean HR increase 2–4 bpm. Persistent sinus tachycardia at >2 visits in 1.6% (vs 0.2% placebo). |
| Fatigue | 5.6% (2.6%) | Generally mild and transient. |
| Constipation | 3.7% (0.7%) | Adequate hydration and fiber typically sufficient. |
| Flatulence | 3.4% (1.4%) | Reflects delayed gastric emptying; self-limited. |
| Abdominal distension | 2.3% (0.7%) | Usually mild and transient. |
| First-degree AV block | 2.3% (0.9%) | Mean PR-interval increase 2–3 ms. Usually clinically silent; relevant only in patients with conduction disease. |
| GERD | 2.0% (0.5%) | Standard reflux measures usually adequate. |
| Eructation (belching) | 1.6% (0.2%) | Often coincident with delayed gastric emptying; self-limited. |
In pediatric patients, injection-site reactions occurred more frequently (3.8–3.9% on dulaglutide vs 2.0% placebo) than in adults (0.5% vs 0.0%).
| Adverse Effect | 1.5 mg | 3 mg | 4.5 mg |
|---|---|---|---|
| Nausea | 13.4% | 15.6% | 16.4% |
| Diarrhea | 7.0% | 11.4% | 10.7% |
| Vomiting | 5.6% | 8.3% | 9.3% |
| Dyspepsia | 2.8% | 5.0% | 2.6% |
| Adverse Effect | Estimated Frequency | Typical Onset | Required Action |
|---|---|---|---|
| Acute pancreatitis (adjudicated) | 1.4 / 1,000 PY (registration pool) | Any time | Discontinue immediately; check lipase; do not restart if confirmed. |
| Severe GI adverse reactions | 2.2% (0.75 mg) / 4.3% (1.5 mg) vs 1.4% placebo | Days–weeks | Hold; manage hydration; reassess. Not recommended in severe gastroparesis. |
| Medullary thyroid carcinoma | Theoretical (one trial case in patient with elevated baseline calcitonin) | Long-term | Avoid in personal/family history of MTC or MEN-2. Evaluate any thyroid mass; routine calcitonin/ultrasound screening not recommended. |
| Acute kidney injury (volume depletion) | Postmarketing reports (frequency unknown) | Days–weeks (in setting of N/V/D) | Hold if volume-depleted; aggressive hydration; reassess renal function. |
| Hypersensitivity / anaphylaxis | Systemic hypersensitivity 0.5%; anaphylaxis/angioedema rare (postmarketing) | Minutes–hours after injection | Emergency care; permanent discontinuation; contraindicated to re-challenge. |
| Severe hypoglycemia (with insulin/SU) | Variable; 0.7% with basal insulin; 2.7–3.4% with prandial insulin | Days–weeks after combination start | Pre-emptively reduce insulin/SU dose; intensify SMBG/CGM. |
| Acute cholecystitis (serious) | 0.5% vs 0.3% placebo (REWIND); cholelithiasis 0.62 vs 0.56 / 100 PY | Months after initiation | Right upper quadrant pain → ultrasound; surgical referral if confirmed. |
| Diabetic retinopathy progression | REWIND: 1.9% vs 1.5% placebo overall; 8.5% vs 6.2% with prior retinopathy | First 6 months (during rapid HbA1c drop) | Baseline retinal exam in pre-existing retinopathy; ophthalmology follow-up. |
| Pulmonary aspiration during anesthesia / deep sedation | Postmarketing reports; frequency unknown | Peri-procedural | Inform anesthesia team. Consider one-week hold before elective procedures requiring sedation. |
| Ileus (postmarketing) | Rare (frequency unknown) | Variable | Discontinue; supportive care; gastroenterology consult. |
| Reason for Discontinuation | Adult AWARD-11 Range (1.5–4.5 mg) | Context |
|---|---|---|
| Nausea | 1.3–1.5% | Most common discontinuation cause; mitigated by slow titration and meal-size reduction. |
| Vomiting | ≤1.3% | Often co-occurs with nausea; persistent vomiting warrants hold and rehydration. |
| Diarrhea | ≤1.0% | Usually transient; rare severe cases requiring discontinuation. |
The single highest-yield intervention is slow titration: maintain 0.75 mg for at least 4 weeks before increasing. Counsel patients to eat smaller portions, stop at the first sign of fullness, avoid high-fat meals, and stay well hydrated. If nausea is moderate-to-severe at 1.5 mg, consider stepping back to 0.75 mg for an additional 2–4 weeks before retrying escalation. Most GI symptoms resolve within 2–4 weeks at a stable dose.
Drug Interactions
Because dulaglutide is metabolized by general proteolytic catabolism rather than the CYP450 system, it has few classic pharmacokinetic interactions. The clinically meaningful interactions cluster into two mechanisms: pharmacodynamic synergy with other glucose-lowering agents, and delayed gastric emptying altering the absorption rate of co-administered oral medications. The FDA PI explicitly notes that dulaglutide 1.5 mg did not alter the absorption of tested oral medications to a clinically relevant degree, but advises monitoring drug levels of agents with a narrow therapeutic index.
Monitoring
Monitoring of dulaglutide therapy combines standard diabetes surveillance with safety screening for class-specific concerns: pancreatitis, gallbladder disease, thyroid signs, retinopathy, and renal function in the context of GI adverse effects.
-
HbA1c
Every 3 months until at goal, then every 6 months
Routine Target generally <7.0% in adults; individualize per ADA 2026 Standards (older adults, limited life expectancy, hypoglycemia history). Re-titrate dulaglutide if not at goal after ≥3 months at maintenance dose. -
Self-Monitored or CGM
Patient-directed; intensified if on insulin or SU
Routine CGM is recommended at diagnosis or thereafter for any patient who may benefit (ADA 2026), particularly those on insulin or sulfonylurea where hypoglycemia risk is elevated. -
Renal Function (Cr, eGFR)
Baseline, then annually; sooner if severe N/V
Trigger-based Volume depletion from prolonged GI symptoms can precipitate AKI (postmarketing reports). Hold dulaglutide and obtain renal panel if a patient becomes dehydrated. -
Body Weight
Each visit
Routine Mean reduction approximately 3 kg with 1.5 mg, 4 kg with 3 mg, and 4.7 kg with 4.5 mg in AWARD-11. Significant gain on therapy warrants reassessment of adherence. -
Pancreatitis Symptoms
Each visit; immediate review if symptomatic
Trigger-based Severe persistent epigastric pain radiating to the back warrants discontinuation, lipase measurement, and imaging. Routine asymptomatic lipase screening is not recommended. -
Thyroid Signs
Each visit
Trigger-based Inquire about new neck mass, dysphagia, hoarseness, or persistent dyspnea. Routine calcitonin screening is of uncertain value per FDA PI; investigate symptomatic findings. -
Diabetic Retinopathy
At diagnosis, then per ADA schedule
Routine Rapid HbA1c improvement may transiently worsen pre-existing retinopathy. Patients with active proliferative disease should have ophthalmology coordination before/during initiation. -
Gallbladder Symptoms
Each visit
Trigger-based RUQ pain, jaundice, or fever → ultrasound. Class-related risk; weight loss may also contribute to gallstone formation. -
Heart Rate / ECG
Baseline (if cardiac history), then each visit
Routine Mean increase 2–4 bpm. First-degree AV block more frequent than placebo (2.3% vs 0.9%); usually clinically silent. Persistent symptomatic tachycardia warrants evaluation. -
Injection Site
Each visit
Routine Inspect for induration, erythema, or lipohypertrophy. Reinforce site rotation between abdomen, thigh, and upper arm. Higher reaction rate in pediatric patients. -
Lipid Panel & BP
Per CV risk management guidelines
Routine Standard CV risk surveillance applies. Modest BP and lipid improvements observed on therapy.
Contraindications & Cautions
Dulaglutide caused a dose-related and treatment-duration-dependent increase in C-cell tumors (adenomas and carcinomas) in rats at clinically relevant exposures. Whether this risk extends to humans, including the development of medullary thyroid carcinoma (MTC), has not been determined.
Dulaglutide is contraindicated in patients with a personal or family history of MTC and in patients with Multiple Endocrine Neoplasia syndrome type 2 (MEN-2). Counsel patients regarding potential symptoms of thyroid tumors (neck mass, dysphagia, dyspnea, persistent hoarseness). Routine monitoring of serum calcitonin or thyroid ultrasound is of uncertain value for early MTC detection in patients on dulaglutide and may increase the risk of unnecessary procedures.
Absolute Contraindications
- Personal or family history of medullary thyroid carcinoma (MTC) — boxed-warning contraindication.
- Multiple Endocrine Neoplasia syndrome type 2 (MEN-2) — boxed-warning contraindication.
- Prior serious hypersensitivity to dulaglutide or any product excipients (e.g., anaphylaxis, angioedema).
Not Recommended (per FDA Labeling)
- Severe gastroparesis — FDA labeling explicitly states dulaglutide is not recommended (Section 5.6, 2024 update).
- Type 1 diabetes mellitus — not effective for absolute insulin deficiency.
- Diabetic ketoacidosis — insulin is the cornerstone of treatment.
Relative Contraindications (Specialist Input Recommended)
- History of pancreatitis — case-by-case decision; class causality is not firmly established but caution is warranted given postmarketing reports of severe pancreatitis.
- Active proliferative diabetic retinopathy or recent intraocular intervention — coordinate with ophthalmology before initiation, given potential for transient worsening with rapid glycemic improvement.
- Pregnancy — animal studies show fetal harm at clinically relevant exposures; insulin is the preferred therapy. Discontinue at conception planning where feasible.
- Severe hepatic impairment — limited clinical experience; specialist co-management appropriate.
Use with Caution
- Mild-to-moderate gastroparesis — start at 0.75 mg with prolonged titration; monitor symptoms closely.
- History of cholelithiasis or gallbladder disease — class-related risk of cholecystitis and gallstones.
- Concomitant insulin or sulfonylureas — adjust the secretagogue/insulin dose to mitigate hypoglycemia.
- Recent or active acute kidney injury — ensure euvolemia before resuming or initiating; manage GI symptoms aggressively.
- Older adults with multiple comorbidities — heightened vigilance for unintended weight loss, dehydration, and fall risk. REWIND included a substantial proportion of patients ≥65 years (53%) without overall safety concerns.
- Pre-procedural fasting / elective surgery — consider holding dulaglutide approximately one week prior when sedation or general anesthesia is planned, given delayed gastric emptying and aspiration risk (per ASA and 2024 multi-society guidance). Always inform anesthesia team of GLP-1 RA use.
- Breastfeeding — no human data; balance maternal need against unknown infant exposure.
Patient Counselling
Purpose of Therapy
Explain that dulaglutide is a once-weekly injection that helps the body release insulin when blood sugar is high, reduces appetite, and slows stomach emptying. For patients with type 2 diabetes who have heart disease or are at high cardiovascular risk, the 1.5 mg dose has been shown to lower the chance of heart attack and stroke. Most patients will lose some weight on therapy — typically a few kilograms over several months — though weight loss is not the primary indication.
How to Take
The pen is single-use and prefilled. Inject under the skin of the abdomen, thigh, or back of the upper arm on the same day each week, at any time of day, with or without food. Rotate injection sites each week. Store unused pens refrigerated at 2–8°C; once in use, the pen may be kept at room temperature (below 30°C) for up to 14 days. Do not freeze or shake. If a dose is missed and there are at least 3 days until the next scheduled dose, take it as soon as remembered; otherwise skip it. The day of the week may be changed if at least 3 days have passed since the last injection.
Sources
- U.S. Food and Drug Administration. Trulicity (dulaglutide) prescribing information (Reference ID: 5598400, revised May 2025). Eli Lilly and Company. accessdata.fda.gov Definitive U.S. labeling — primary source for boxed warning, indications, dosing, adverse reaction tables (Tables 1–3), severe gastroparesis warning (Section 5.6, Nov 2024) and pulmonary aspiration warning (Section 5.9, Nov 2024).
- European Medicines Agency. Trulicity (dulaglutide) Summary of Product Characteristics. ema.europa.eu European labeling reference; useful cross-check for non-US jurisdictions.
- Gerstein HC, Colhoun HM, Dagenais GR, et al; REWIND Investigators. Dulaglutide and cardiovascular outcomes in type 2 diabetes (REWIND): a double-blind, randomised placebo-controlled trial. Lancet. 2019;394(10193):121–130. doi.org/10.1016/S0140-6736(19)31149-3 Pivotal cardiovascular outcomes trial (n=9,901; HR 0.88, 95% CI 0.79–0.99; p=0.026 for MACE) — basis for the FDA cardiovascular indication, with 69% in primary prevention.
- Frias JP, Bonora E, Nevarez Ruiz L, et al. Efficacy and safety of dulaglutide 3.0 mg and 4.5 mg versus dulaglutide 1.5 mg in metformin-treated patients with type 2 diabetes in a randomized controlled trial (AWARD-11). Diabetes Care. 2021;44(3):765–773. doi.org/10.2337/dc20-1473 Dose-finding trial supporting the higher 3 mg and 4.5 mg dosing options. Source for AWARD-11 GI adverse-reaction rates referenced in FDA PI Table 2.
- Arslanian SA, Hannon T, Zeitler P, et al; AWARD-PEDS Investigators. Once-weekly dulaglutide for the treatment of youths with type 2 diabetes. N Engl J Med. 2022;387(5):433–443. doi.org/10.1056/NEJMoa2204601 Pediatric registration trial (n=154; 26-week double-blind + 26-week extension) supporting approval in patients aged 10 years and older. Demonstrated HbA1c benefit without significant change in BMI.
- Dungan KM, Povedano ST, Forst T, et al. Once-weekly dulaglutide versus once-daily liraglutide in metformin-treated patients with type 2 diabetes (AWARD-6): a randomised, open-label, phase 3, non-inferiority trial. Lancet. 2014;384(9951):1349–1357. doi.org/10.1016/S0140-6736(14)60976-4 Head-to-head comparison with liraglutide demonstrating non-inferior HbA1c reduction with once-weekly convenience.
- Wysham C, Blevins T, Arakaki R, et al. Efficacy and safety of dulaglutide added onto pioglitazone and metformin versus exenatide in type 2 diabetes (AWARD-1). Diabetes Care. 2014;37(8):2159–2167. doi.org/10.2337/dc13-2760 Foundational AWARD-program trial supporting initial efficacy and tolerability profile.
- American Diabetes Association Professional Practice Committee. Pharmacologic Approaches to Glycemic Treatment: Standards of Care in Diabetes—2026. Diabetes Care. 2026;49(Suppl 1):S183–S215. doi.org/10.2337/dc26-S009 Authoritative U.S. guidance on GLP-1 RA placement in T2DM care, including organ-specific algorithm priorities (CKD, ASCVD, HF, MASLD/MASH).
- Davies MJ, Aroda VR, Collins BS, et al. Management of hyperglycaemia in type 2 diabetes, 2022. A consensus report by the ADA and EASD. Diabetes Care. 2022;45(11):2753–2786. doi.org/10.2337/dci22-0034 Joint ADA-EASD consensus shaping current GLP-1 RA prioritization for ASCVD, HF, and CKD comorbidities.
- Kidney Disease: Improving Global Outcomes (KDIGO) Diabetes Work Group. KDIGO 2022 Clinical Practice Guideline for Diabetes Management in Chronic Kidney Disease. Kidney Int. 2022;102(5S):S1–S127. kdigo.org Reference for GLP-1 RA selection in patients with diabetes and CKD, including AWARD-7-derived no-dose-adjustment guidance.
- Joshi GP, Abdelmalak BB, Weigel WA, et al. American Society of Anesthesiologists consensus-based guidance on preoperative management of patients (adults and children) on glucagon-like peptide-1 (GLP-1) receptor agonists. ASA, June 2023; updated November 2024. asahq.org Guidance suggesting holding weekly GLP-1 RAs one week prior to elective procedures requiring anesthesia or deep sedation.
- Kindel TL, Wang AY, Wadhwa A, et al. Multisociety clinical practice guidance for the safe use of glucagon-like peptide-1 receptor agonists in the perioperative period. Surg Obes Relat Dis. 2024;20(12):1183–1186. doi.org/10.1016/j.soard.2024.08.033 2024 multi-society guidance (AGA/ASMBS/ISPCOP/SAGES; ASA Affirmation of Value) on shared decision-making and risk mitigation for perioperative GLP-1 RA use.
- Drucker DJ. Mechanisms of action and therapeutic application of glucagon-like peptide-1. Cell Metab. 2018;27(4):740–756. doi.org/10.1016/j.cmet.2018.03.001 Comprehensive review of GLP-1 receptor biology and downstream effects on glucose homeostasis, appetite, and the cardiovascular system.
- Glaesner W, Vick AM, Millican R, et al. Engineering and characterization of the long-acting glucagon-like peptide-1 analogue LY2189265, an Fc fusion protein. Diabetes Metab Res Rev. 2010;26(4):287–296. doi.org/10.1002/dmrr.1080 Original molecular design paper describing the IgG4 Fc fusion strategy that underlies once-weekly dosing.
- Geiser JS, Heathman MA, Cui X, et al. Clinical pharmacokinetics of dulaglutide in patients with type 2 diabetes: analyses of data from clinical trials. Clin Pharmacokinet. 2016;55(5):625–634. doi.org/10.1007/s40262-015-0338-3 Population PK analysis informing dosing recommendations across body weight, age, and renal function strata.
- Tuttle KR, Lakshmanan MC, Rayner B, et al. Dulaglutide versus insulin glargine in patients with type 2 diabetes and moderate-to-severe chronic kidney disease (AWARD-7): a multicentre, open-label, randomised trial. Lancet Diabetes Endocrinol. 2018;6(8):605–617. doi.org/10.1016/S2213-8587(18)30104-9 Key trial supporting the absence of dose adjustment in moderate-to-severe CKD, including reduced eGFR decline observations.
- Frias JP, Bonora E, Tinahones FJ, et al. Effect of dulaglutide 3.0 and 4.5 mg on weight in patients with type 2 diabetes: exploratory analyses of AWARD-11. Diabetes Obes Metab. 2021;23(10):2242–2250. doi.org/10.1111/dom.14465 Source for dose-stratified weight outcomes (1.5 mg: −3.1 kg; 3 mg: −4.0 kg; 4.5 mg: −4.7 kg at 36 weeks).