J Curr Pharmacol

Journal of Current Pharmacology, ISSN NoIssnPrint print, 0000-0000 online, Open Access

Article copyright, the authors; Journal compilation copyright, J Curr Pharmacol and Elmer Press Inc

Journal website https://jcp.elmerpub.com

Review

Volume 1, 2026, e5

Beyond the Procedure Day: Chronic Gastrointestinal and Nutritional Sequelae of Sustained Glucagon-Like Peptide-1 Receptor Agonist Therapy: Implications for the Internist

↓ Figure 1. Longitudinal surveillance and management pathway for the patient on sustained GLP-1 RA therapy. The pathway has three color-coded phases (initiation, maintenance surveillance, and escalation/response) and is supported by the overarching goals of therapy and team-based care. GI: gastrointestinal; GLP-1 RA: glucagon-like peptide-1 receptor agonist.

↓ **Table 1.** Chronic Gastrointestinal and Nutritional Consequences of Sustained GLP-1 RA Therapy: Mechanism, At-Risk Subgroups, and Suggested Monitoring
Domain/manifestation	Proposed mechanism	Highest-risk subgroups	Suggested monitoring
C_max: maximum plasma concentration; DXA: dual-energy X-ray absorptiometry; GLP-1 RA: glucagon-like peptide-1 receptor agonist; INR: international normalized ratio.
Chronic nausea/early satiety	Persistent delayed gastric emptying; central anorexigenic signaling	Early titration phase; higher doses	Symptom review each visit; slow titration; dose moderation
GLP-1-associated gastric stasis (gastroparesis-like)	Marked, sustained deceleration of gastric emptying	Pre-existing diabetic autonomic neuropathy	Relate onset to dosing; gastric emptying study if refractory; consider dose hold
Altered absorption of concomitant oral drugs	Delayed gastric emptying lowers C_max and delays absorption, most marked after initiation and dose escalation	Narrow-therapeutic-index drugs (warfarin, levothyroxine); oral contraceptives with tirzepatide	Medication review at each escalation; INR or thyroid function after dose changes; non-oral or barrier contraception for 4 weeks with tirzepatide
Protein-energy inadequacy	Sustained appetite suppression and reduced intake	Older adults; frailty; restrictive eating	Weight trajectory; dietary protein intake; nutritional review
Micronutrient deficiency	Reduced and selective intake	Prior bariatric surgery; restrictive diets; prolonged therapy	Periodic iron, vitamin B12, vitamin D, folate
Lean-mass loss/sarcopenia	Rapid weight loss without adequate protein or resistance exercise	Older, frail, low baseline muscle mass	Grip strength/gait speed; body composition where available
Bone mineral density loss	Weight-loss-associated bone turnover	Postmenopausal women; older adults	DXA in high-risk patients; weight-bearing exercise
Cholelithiasis/cholecystitis	Rapid weight loss; reduced gallbladder motility and bile stasis	Rapid responders; higher doses; prior gallstones	Counsel on symptoms; right-upper-quadrant ultrasound if symptomatic
Acute pancreatitis (uncertain signal)	Incretin effect; causality not established	Prior pancreatitis; hypertriglyceridemia	Discontinue and assess (lipase) if suspected

↓ Table 1. Chronic Gastrointestinal and Nutritional Consequences of Sustained GLP-1 RA Therapy: Mechanism, At-Risk Subgroups, and Suggested Monitoring

Domain/manifestation

Proposed mechanism

Highest-risk subgroups

Suggested monitoring

C_max: maximum plasma concentration; DXA: dual-energy X-ray absorptiometry; GLP-1 RA: glucagon-like peptide-1 receptor agonist; INR: international normalized ratio.

Chronic nausea/early satiety

Persistent delayed gastric emptying; central anorexigenic signaling

Early titration phase; higher doses

Symptom review each visit; slow titration; dose moderation

GLP-1-associated gastric stasis (gastroparesis-like)

Marked, sustained deceleration of gastric emptying

Pre-existing diabetic autonomic neuropathy

Relate onset to dosing; gastric emptying study if refractory; consider dose hold

Altered absorption of concomitant oral drugs

Delayed gastric emptying lowers C_max and delays absorption, most marked after initiation and dose escalation

Narrow-therapeutic-index drugs (warfarin, levothyroxine); oral contraceptives with tirzepatide

Medication review at each escalation; INR or thyroid function after dose changes; non-oral or barrier contraception for 4 weeks with tirzepatide

Protein-energy inadequacy

Sustained appetite suppression and reduced intake

Older adults; frailty; restrictive eating

Weight trajectory; dietary protein intake; nutritional review

Micronutrient deficiency

Reduced and selective intake

Prior bariatric surgery; restrictive diets; prolonged therapy

Periodic iron, vitamin B12, vitamin D, folate

Lean-mass loss/sarcopenia

Rapid weight loss without adequate protein or resistance exercise

Older, frail, low baseline muscle mass

Grip strength/gait speed; body composition where available

Bone mineral density loss

Weight-loss-associated bone turnover

Postmenopausal women; older adults

DXA in high-risk patients; weight-bearing exercise

Cholelithiasis/cholecystitis

Rapid weight loss; reduced gallbladder motility and bile stasis

Rapid responders; higher doses; prior gallstones

Counsel on symptoms; right-upper-quadrant ultrasound if symptomatic

Acute pancreatitis (uncertain signal)

Incretin effect; causality not established

Prior pancreatitis; hypertriglyceridemia

Discontinue and assess (lipase) if suspected