Introduction

Diabetes mellitus has become one of the most important chronic diseases encountered in surgical practice. According to recent literature, approximately one in five surgical patients has diabetes, while many additional patients present with prediabetes or undiagnosed disease.

The rapid expansion of newer antidiabetic therapies, including glucagon-like peptide-1 receptor agonists (GLP-1 RAs), sodium-glucose cotransporter-2 inhibitors (SGLT2 inhibitors), and dipeptidyl peptidase-4 inhibitors (DPP-4 inhibitors), has transformed diabetes management. However, these medications also create new challenges for anesthesiologists and perioperative clinicians.

A newly published review highlights evolving recommendations and emerging evidence regarding the perioperative management of these therapies.

Why diabetes matters during surgery

Surgery and anesthesia trigger a physiological stress response that can significantly disrupt glucose regulation.

This response increases:

• Catecholamine release
• Cortisol secretion
• Inflammatory cytokine production
• Hepatic glucose output

As a result, perioperative hyperglycemia may develop and contribute to:

• Surgical site infections
• Delayed wound healing
• Longer hospital stays
• Increased postoperative complications
• Higher mortality risk

Because of these risks, perioperative glucose management remains a cornerstone of surgical care.

Current recommendations for preoperative assessment

Recent guidance recommends that patients with diabetes undergo hemoglobin A1c (HbA1c) testing within three months before surgery.

Key recommendations

• Obtain HbA1c within 3 months of surgery.
• Consider postponing elective surgery when HbA1c exceeds 8%.
• Do not delay urgent or emergency surgery solely because of elevated HbA1c.
• Treat blood glucose levels above 180 mg/dL with insulin.

These measures help reduce perioperative complications and improve surgical outcomes.

Metformin: a changing perspective

For many years, clinicians frequently stopped metformin before surgery because of concerns regarding lactic acidosis.

However, more recent evidence challenges this practice.

How metformin works

Metformin:

• Suppresses hepatic gluconeogenesis
• Reduces glycogenolysis
• Improves insulin sensitivity
• Decreases intestinal glucose absorption

What the latest evidence shows

Large population studies have not demonstrated an increased risk of lactic acidosis among metformin users. As a result, recent cardiovascular and perioperative guidelines suggest that continuing metformin throughout the perioperative period is reasonable in many patients.

Clinical implications

Potential benefits of continuing metformin include:

• Improved glycemic stability
• Reduced glucose fluctuations
• Simpler medication management
• Lower risk of perioperative hyperglycemia

GLP-1 receptor agonists: the most debated drugs in anesthesia

Perhaps no drug class has generated more perioperative discussion than GLP-1 receptor agonists.

Popular medications include:

• Semaglutide (Ozempic, Rybelsus)
• Dulaglutide (Trulicity)
• Exenatide
• Tirzepatide (Mounjaro)

Why are these medications important?

GLP-1 receptor agonists provide:

• Excellent glucose control
• Significant weight loss
• Reduced cardiovascular risk
• Lower rates of major adverse cardiovascular events

Tirzepatide, which targets both GLP-1 and GIP receptors, has demonstrated even greater metabolic benefits in clinical trials.

The aspiration concern

The major perioperative concern involves delayed gastric emptying.

Because GLP-1 drugs slow gastric emptying, patients may retain stomach contents longer than expected. This raises theoretical concerns about:

• Regurgitation during anesthesia
• Pulmonary aspiration
• Aspiration pneumonia

Early recommendations suggested withholding these medications before surgery.

However, more recent evidence has altered that perspective.

New evidence on aspiration risk

A large 2025 meta-analysis involving more than 185,000 patients found:

• Increased residual gastric contents in GLP-1 users
• No statistically significant increase in pulmonary aspiration events

Another large study involving nearly 600,000 patients reported:

• Extremely low aspiration rates overall
• Lower observed aspiration rates among GLP-1 users compared with non-users

What guidelines now recommend

Most current international guidelines support:

• Continuing GLP-1 therapy in most patients
• Individualized risk assessment
• Use of gastric ultrasound when available
• Additional precautions in patients with severe gastrointestinal symptoms

Which patients may require extra caution?

Higher-risk patients include those with:

• Severe nausea
• Persistent vomiting
• Abdominal pain
• Gastroparesis
• Bowel dysmotility
• Parkinson disease
• Recent dose escalation of GLP-1 therapy

For these individuals, clinicians may consider:

1. Extended fasting protocols.
2. Gastric ultrasound evaluation.
3. Delaying elective surgery when appropriate.
4. Rapid-sequence induction techniques during anesthesia.

SGLT2 inhibitors: balancing benefits and risks

SGLT2 inhibitors have become increasingly important because they offer benefits extending beyond glucose control.

Common agents include:

• Empagliflozin
• Dapagliflozin
• Canagliflozin
• Ertugliflozin

Benefits of SGLT2 inhibitors

These medications provide:

• Improved glycemic control
• Cardiovascular protection
• Renal protection
• Heart failure benefits
• Reduced hospitalization rates in selected populations

The concern: euglycemic diabetic ketoacidosis

The principal perioperative concern is euglycemic diabetic ketoacidosis (eDKA).

Unlike traditional diabetic ketoacidosis, eDKA may occur despite relatively normal blood glucose levels.

Symptoms may include

• Nausea
• Vomiting
• Abdominal pain
• Fatigue
• Tachypnea
• Metabolic acidosis

Because blood glucose may appear relatively normal, diagnosis can be delayed.

Current recommendations for SGLT2 inhibitors

Most contemporary guidelines recommend:

Before surgery

• Stop SGLT2 inhibitors approximately 3–4 days before surgery.

After surgery

• Restart once the patient:
  • Is clinically stable
  • Has resumed normal nutrition
  • Shows no evidence of ketoacidosis

Emerging evidence challenges existing assumptions

Several large studies published recently have produced surprising findings.

Researchers observed:

• Lower postoperative mortality among SGLT2 inhibitor users
• Reduced acute kidney injury rates
• Potential organ-protective effects
• Mixed findings regarding ketoacidosis risk

One randomized pilot study in cardiac surgery patients even found:

• Less postoperative fluid accumulation
• Lower rates of acute kidney injury
• No observed ketoacidosis events

These findings suggest that future recommendations may become more individualized rather than universally stopping therapy.

DPP-4 inhibitors: the overlooked class

DPP-4 inhibitors often receive less attention than GLP-1 or SGLT2 therapies.

Common examples include:

• Sitagliptin
• Linagliptin
• Saxagliptin
• Alogliptin

Benefits

These medications:

• Improve glycemic control
• Have low hypoglycemia risk
• Are generally well tolerated
• Serve as alternatives when metformin cannot be used

Emerging research

New studies suggest DPP-4 inhibition may:

• Reduce systemic inflammation
• Improve endothelial function
• Stabilize vascular barriers
• Potentially protect organs during surgical stress

However, larger clinical trials are still needed.

Personalized perioperative care is the future

The review emphasizes that modern diabetes management requires individualized decision-making.

Rather than applying identical rules to every patient, clinicians should evaluate:

• Type of diabetes medication
• Surgical complexity
• Aspiration risk
• Renal function
• Cardiovascular disease
• Nutritional status
• Glycemic control
• Comorbid conditions

The goal is to preserve the proven benefits of these medications while minimizing perioperative risks.

Conclusion

The landscape of perioperative diabetes care is evolving rapidly. As the use of GLP-1 receptor agonists, SGLT2 inhibitors, and DPP-4 inhibitors continues to grow, anesthesiologists must remain informed about both the benefits and potential perioperative risks associated with these therapies.

Current evidence increasingly supports individualized, risk-based management rather than routine discontinuation of newer diabetes medications. While concerns such as aspiration risk and euglycemic ketoacidosis remain important, emerging data suggest that many of these drugs may also provide meaningful perioperative benefits, including cardiovascular and renal protection.

The overarching message from the latest review is clear: perioperative diabetes care should be personalized, evidence-based, and continuously updated as new research emerges.

Reference: Riesemann S et al. Perioperative anesthesia care for patients with diabetes mellitus: a review of current literature with focus on oral antidiabetic medication. Curr Opin Anaesthesiol. 2026;39:381-389.  

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