Diabetes Management in the Hospitalized Patient

US Pharm. 2024;49(3):HS8-HS12.

ABSTRACT: Diabetic patients often present to the hospital with chief complaints not related to their diabetic state. Pharmacists play a major role in establishing an appropriate insulin regimen for patients with type 1 diabetes mellitus and type 2 diabetes mellitus. For example, pharmacists play an integral role in the management of hyperglycemia for patients with diabetes. Particularly in the acute care and critical care settings, being in tune with potential procedures and changes in nutritional status/intake empowers a pharmacist to make proactive changes to a patient’s insulin regimen, avoiding hypoglycemic events. The American Diabetes Association and the Endocrine Society have clinical practice guidelines to help the clinician with inpatient diabetic management.

Patients with type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM) are often admitted to the hospital. These patients may be admitted for the treatment of conditions not associated with diabetes or may be admitted for the treatment of diabetic complications, including diabetic ketoacidosis, hyperglycemic hyperosmolar syndrome, hypoglycemia, infections, and more. Despite the reason for admission, diabetic patients must have appropriate control of blood glucose (BG) to mitigate increased risk of infection due to immune and neutrophil function impairment, electrolyte disturbances, dehydration, glycosuria, caloric loss, and hyper- or hypoglycemic emergencies. Avoiding BG variability while an inpatient may help prevent adverse events and improve clinical outcomes. Alterations in BG due to concomitant medications (such as corticosteroids), changes in diet, and the potential for insulin resistance from various causes lead to fluctuations in BG that may be vastly different than the patient’s typical BG levels.

Overview of Diabetic Goals in the Hospital Setting

The Standards of Medical Care in Diabetes provided by the American Diabetes Association (ADA) recommends a hemoglobin A1C test on all patients with diabetes or hyperglycemia (BG >140 mg/dL) admitted to the hospital if not performed in the prior 3 months.¹ This recommendation stems from the fact that high hemoglobin A1C levels are associated with poor clinical outcomes in hospitalized patients. Additionally, this may help clinicians determine if hyperglycemia is due to undiagnosed diabetes or stress hyperglycemia. Identifying an elevated A1C during hospitalization provides an opportunity to tailor appropriate diabetes management at hospital discharge. The predictive value of admission A1C has also been shown to be a predictor of glycemic control and response to insulin treatment with basal-bolus during hospitalizations in patients with T2DM.² In a study combining inpatient data from four randomized, controlled trials, patients with a higher A1C on admission were less likely to achieve glycemic control compared with those with an A1C ≤7% despite appropriate incremental increase in insulin therapy.²

The ADA recommends initiating insulin therapy for the treatment of persistent hyperglycemia starting at a threshold of ≥180 mg/dL when BG is checked on two occasions. After insulin therapy has been initiated, a goal BG of 140 mg/dL to 180 mg/dL is currently recommended for both critically ill and noncritically ill patients.¹ It is worth noting that patients who are critically ill post surgery or post cardiac surgery may be treated with more strict BG goals of 110 mg/dL to 140 mg/dL, as long as hypoglycemia can be avoided.¹ This recommendation stems from the fact that patients with diabetes undergoing cardiac surgery have a higher perioperative morbidity and mortality, significantly reduced long-term survival, and less freedom from recurrent episodes of angina.³ Additionally, concerns for sternal wound infection and postoperative healing due to uncontrolled BG may lead clinicians to target a lower BG goal in this patient population. The landmark trial by Van den Bergh et al showed that intensive insulin therapy to maintain BG <110 mg/dL reduced mortality by 40% compared with a standard approach of targeting BG 180 mg/dL to 215 mg/dL among critically ill patients in the surgical ICU.⁴ However, a subsequent trial (NICE-SUGAR) showed that critically ill patients randomized to intensive glycemic control of <110 mg/dL actually had slightly higher mortality (27.5% vs. 25%) compared with a BG goal of 140 mg/dL to 180 mg/dL.⁴ These trials taken together show that insulin treatment in the inpatient setting to control BG has immediate effects in hospitalized patients, but strict BG control may have adverse consequences.^4,5

Glucose-Lowering Treatment in Hospitalized Patients

Insulin therapy is the gold standard for inpatient treatment of hyperglycemia. Insulin allows the body to utilize glucose for energy, while also decreasing hepatic gluconeogenesis and stimulating glycogen synthesis. Basal insulin or a basal plus bolus correction insulin regimen is recommended by the ADA for treatment in hospitalized patients with poor oral intake or those who are taking nothing by mouth.¹ Basal, prandial, and correction insulin are the preferred treatments for hospitalized patients with good nutritional intake.¹ Insulin should align with meals, and point-of-care glucose testing should be performed immediately before meals. The ADA strongly discourages the use of only a sliding-scale insulin regimen.¹ A meta-analysis showed that a basal-bolus insulin strategy results in better short-term glycemic control compared with a sliding-scale insulin regimen.⁶

Type 1 Diabetes Mellitus

For patients with T1DM, it is prudent to ensure that dosing insulin based solely on premeal glucose levels does not occur, as this would not account for basal insulin requirements. As T1DM results in insulin deficiency, patients with T1DM require lifelong insulin replacement therapy from the time of diagnosis.⁷ Insulin therapy in T1DM patients usually involves multiple daily injections consisting of basal and prandial insulin. There are various modes of administration of insulin, including syringe, pen, prefilled pen, and pump. Basal insulin includes detemir, glargine, and degludec, while prandial insulins include rapid-acting insulin consisting of lispro, aspart, glulisine, and short-acting insulin consisting of regular insulin.⁷ Although premixed insulins are available, they are not recommended for the treatment of T1DM considering that there is an inability to adjust the basal and prandial requirements.⁷ Typically, basal insulin doses are based on body weight, with some evidence suggesting that patients with renal insufficiency should be treated with lower doses of insulin.¹ In a randomized trial, the reduction of initial basal insulin weight-based dosing in hospitalized patients with diabetes and renal insufficiency reduced the frequency of hypoglycemia by 50%.⁸ Patients with T1DM should always be treated with basal insulin. Pharmacists can educate providers when there appears to be a lapse in basal insulin orders for hospitalized patients.

Type 2 Diabetes Mellitus

As with T1DM, insulin is the gold standard for the management of hyperglycemia in hospitalized patients with T2DM.¹ Unlike those with T1DM, patients with T2DM may not necessarily require basal insulin—their regimen should be tailored to patient specific factors, including nutritional status and severity of illness. The ADA guidelines also note that basal-bolus regimens are generally preferred over inpatient use of insulin mixtures, such as 75/25 or 70/30, citing a study that found that mixtures resulted in similar glycemic control but greater frequency of hypoglycemia as opposed to basal-bolus regimens in hospitalized patients with T2DM.^1,9 For patients who utilize an insulin pump at home, it may be reasonable to continue self-management inpatient under specific conditions, including adequate oral intake, stable insulin requirements, and maintaining both the cognitive and physical ability to do so.¹ If the hospital length of stay is anticipated to be longer than 1 to 2 days, the guidelines recommend transitioning to a basal-bolus regimen prior to discontinuation of the pump.¹⁰ Nutrition status is an important consideration when determining an appropriate insulin regimen. For patients receiving enteral nutrition, it is recommended that most patients continue receiving basal insulin in addition to scheduled insulin to account for the nutritional component, typically calculated as 1 unit of insulin for every 10 g to 15 g of carbohydrates. This can be accomplished by administering NPH insulin every 8 to 12 hours or with regular insulin administered every 6 hours. Patients should also be administered correctional insulin every 6 hours. In the event that enteral nutrition is stopped or interrupted, patients should be started on a 10% dextrose infusion to prevent hypoglycemia until the regimen can be appropriately adjusted.¹ For patients receiving parenteral nutrition, regular insulin may be added to the solution, with a typical recommended starting dose of 1 unit of regular insulin for every 10 g of dextrose.^1,11 However, this practice is often institution-specific.

In critically ill patient populations, it may be prudent to utilize IV insulin infusions initially over basal insulin regimens, particularly in hemodynamically unstable patients or those with changing clinical status. Once stabilized clinically, patients may be transitioned to an SC regimen.¹² When transitioning, patients should receive a basal dose of SC insulin 2 hours before the IV infusion is discontinued to mitigate dysglycemia.^1,13,14

Noninsulin Therapies

While insulin is the standard of care for managing hyperglycemia in hospitalized patients, there has been research into the utilization of noninsulin therapies, including dipeptidyl peptidase-4 (DPP-4) inhibitors and glucagon-like peptide-1 (GLP-1) agonists.

Sitagliptin and linagliptin, both DPP-4 inhibitors, have been evaluated in randomized clinical trials. In a multicenter pilot study, general medicine and surgery patients with T2DM treated with diet, an oral antidiabetic agent, or low-dose total daily insulin (≤0.4 units/kg/day) were randomized to receive either monotherapy sitagliptin, sitagliptin plus insulin glargine, or a basal-bolus insulin regimen with glargine and lispro. There was no difference in glycemic control, hospital length of stay, or hypoglycemic episodes between the groups. The authors also found that total daily insulin dosage and the number of injections were significantly less in the sitagliptin groups (P <.001 for both), concluding that sitagliptin alone or in combination with insulin glargine may be a safe and effective alternative to a traditional basal-bolus regimen.¹⁵ Linagliptin was studied in noncardiac surgery patients who, similarly to the previous study, were treated with diet, an oral agent, or a lower total daily insulin dosage (≤0.5 units/kg/day).¹⁶ Patients were randomized to receive either linagliptin or basal-bolus with glargine and rapid-acting insulin with meals. Mean daily BG levels were higher in the linagliptin group (P = .03), and this seemed to be driven primarily by patients who had BG ≥11.1 mmol/L (10.9 ± 2.6 in the linagliptin arm vs. 9.2 ± 2.2 mmol/L in the basal bolus arm, P <.001). There were fewer episodes of hypoglycemia in the linagliptin arm, leading the authors to conclude that linagliptin may be a safe and effective alternative regimen for hospitalized patients with T2DM and moderate hyperglycemia (BG <11.1 mmol/L).

Dulaglutide and exenatide—GLP-1 agonists—have also been evaluated in randomized, controlled trials. Dulaglutide was evaluated in a pilot study including noncritically ill hospitalized patients who were randomized to receive either basal plus correctional mealtime insulin or basal plus correction insulin with dulaglutide.¹⁷ The insulin plus dulaglutide arm was found to have less glucose variability, defined as a percentage of measurements within the range set by the authors of 100 mg/dL to 180 mg/dL (44% vs. 56%, P <.001). They also found a lower incidence of both hyper- and hypoglycemia in the insulin plus dulaglutide arms (P <.001). Exenatide was studied in a trial that randomized general medicine or surgery patients with T2DM to receive either exenatide alone, exenatide plus basal insulin, or a basal-bolus insulin regimen.¹⁸ The authors found that exenatide plus basal insulin achieved a higher percentage of BG levels within the goal range of 70 mg/dL and 180 mg/dL compared with exenatide monotherapy and basal-bolus (78% vs. 62% and 63%, respectively, P = .023). A greater number of patients in the exenatide arms experienced nausea or vomiting, and 6% of patients had exenatide discontinued as a result.

The ADA guidelines acknowledge these findings; however, they do not provide specific recommendations on utilizing these agents in the inpatient setting. The ADA guidelines also note the FDA bulletin stating that providers should consider discontinuing saxagliptin and alogliptin, two other DPP-4 inhibitors, in patients who develop heart failure given a potential increased risk of worsening heart failure.^1,19 The Endocrine Society guidelines recommend that insulin therapy be used over noninsulin options in hospitalized patients, although they note that DPP-4 inhibitors may be considered in patients with mild hyperglycemia.¹⁰ The recommendation of insulin over other therapies also encompasses metformin and sulfonylureas. Metformin is generally withheld given the risk of accumulation that can occur with renal dysfunction, and sulfonylureas are withheld given the risk of hypoglycemia, especially in patients with no or reduced dietary intake.²⁰ The ADA guidelines also comment on sodium-glucose cotransporter 2 inhibitors, stating that they should not be used routinely in hospitalized patients for diabetes management until more evidence is available to establish safety and efficacy.¹

Role of the Pharmacist

Pharmacists play an integral role in the management of hyperglycemia for patients with diabetes. Particularly in the acute care and critical care settings, being in tune with potential procedures and changes in nutritional status/intake empowers a pharmacist to make proactive changes to a patient’s insulin regimen, avoiding hypoglycemic events. It is important to be aware of other risk factors as well, including acute kidney injury and inappropriate timing of BG checks and/or insulin administration, as well as changes in medications that impact BG levels, such as corticosteroid administration.¹ When hypoglycemia does occur, it is important to ensure that it is adequately treated, reevaluated, and the cause of the episode identified to prevent it from occurring again—all roles that pharmacists are well-equipped to fulfill.

REFERENCES

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19. FDA. FDA drug safety communication: FDA adds warnings about heart failure risk to labels of type 2 diabetes medicines containing saxagliptin and alogliptin. March 7, 2018. www.fda.gov/drugs/drug-safety-and-availability/fda-drug-safety-communication-fda-adds-warnings-about-heart-failure-risk-labels-type-2-diabetes?attorney_name=Kirby+Farris. Accessed August 30, 2023.
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