Key points for patients taking an SGLT2 inhibitor: ● Adequate fluid intake is necessary to prevent dehydration and increased risk for diabetic ketoacidosis while using an SGLT2 inhibitor. ● SGLT2 inhibitors should be stopped 48 to 72 hours before planned surgery. ● If a patient develops diarrhea, vomiting, or dehydration, the SGLT2i should be held/skipped until symptoms resolve. ● Patients should be made aware of symptoms of diabetic ketoacidosis (nausea, vomiting, abdominal pain, weakness)
and that this can occur with blood glucose readings in the 150 to 250 mg/dL range. Patients should seek urgent medical attention with any of these symptoms. ● If taking a diuretic, the dose may need to be decreased when starting an SGLT2 inhibitor. ● If taking insulin, total daily insulin dose may be decreased by 20% when starting an SGLT2 inhibitor. ● Patients should be advised to monitor and report any symptoms of a genital fungal infection, urinary tract infection, or foot wound.
DIPEPTIDYL PEPTIDASE-4 (DPP-4) INHIBITORS
Dipeptidyl peptidase-4 (DPP-4) inhibitors are a class of noninsulin antihyperglycemic agents that prevent the inactivation of endogenous incretin hormones. Incretins are hormones produced in the GI tract following the ingestion of food. Two major incretin hormones are the gastric inhibitory polypeptide (GIP) and glucagon-like peptide (GLP-1). Both hormones work to increase insulin secretion following a meal. In addition, both hormones work to advance beta-cell proliferation. Four DDP-4 Mechanism of action Circulating levels of GIP and GLP-1 are low in a fasting state and rapidly rise following a meal. GIP and GLP-1 are responsible for advancing beta cell proliferation, while GLP-1 suppresses glucagon secretion, inhibits gastric emptying, and increases satiety. Abnormalities in the incretin system contribute to the progression of type 2 diabetes, with the DPP-4 enzyme Side effects DPP-4 inhibitors are usually well tolerated, with a minimal risk of hypoglycemia and a low occurrence of side effects. The most reported side effects for patients taking DPP-4 inhibitors include nasopharyngitis, headache, urinary tract infection, and upper Dosing of DPP-4 inhibitors Available strengths, starting doses, and titrating doses for DPP-4 inhibitors are displayed in Table 7. Data consistently demonstrate that DPP-4 inhibitors are associated with positive effects on A1C, fasting plasma glucose (FPG), and postprandial glucose (PPG) with achievement of glycemic goals when an incretin mimetic is added to existing treatment regimens. DPP- 4 inhibitors have a weight-neutral effect (see Figure 3), and improvements in beta-cell function are not consistently achieved. DPP-4 inhibitors are recommended as an add-on or to be used in combination with metformin, an SGLT-2, or a thiazolidinedione in patients not achieving glycemic goals. No one DPP-4 inhibitor
inhibitors currently approved by the FDA are sitagliptin (Januvia), saxagliptin (Onglyza), linagliption (Tradjenta), and alogliptin (Nesina). There are several combination drugs that include a DPP-4, including a combination of metformin and a DDP-4, empagliflozin and a DDP-4 and pioglitazone and a DDP-4. Several other DPP-4 inhibitors have been approved by the European Medicine Agency and are available for use in Europe (McKeirnan & Neumiller, 2022). breaking down the endogenous incretin hormones GLP-1 and GIP. DPP-4 inhibitors improve glycemia by prolonging the half-life of endogenously provided GLP-1 and GIP by slowing the inactivation of these hormones. DPP-4 inhibitors are administered orally to increase the concentrations of endogenous GIP and GLP-1 by inhibiting the DPP-4 enzyme.
respiratory infection. The incidence of hypoglycemia is higher when a DPP-4 inhibitor is administered in combination with sulfonylureas (McKeirnan & Neumiller, 2022).
is recommended or preferred over another (McKeirnan & Neumiller, 2022). T2DM is a progressive and chronic disease. Therefore, maintaining glycemic targets with monotherapy is often possible for only a few years, after which combination therapy is necessary. Over the past decade, recommendations have been to use stepwise addition of noninsulin antihyperglycemic agents to metformin to maintain A1C targets. However, recent evidence supports initial and early combination therapy for more rapid attainment of glycemic targets (ElSayed et al., 2023a; Matthews et al., 2019; White, 2022).
Evidence-Based Practice Early use of combination therapy to sustain glycemic variability is critical to delay the onset of diabetes-related complications. Research findings support the use of combination therapy (e.g., vildagliptin efficacy in combination with metformin compared to a sequential addition of other medications over time) to provide greater and durable long-term benefits. Patients receiving an initial combination of metformin and a dipeptidyl peptidase 4 (DPP-4) inhibitor vildagliptin had slower decline of glycemic control compared with metformin alone. Results are not generalized to other noninsulin antihyperglycemic agents. Combination therapy is considered in patients presenting with A1C levels 1.5% to 2.0% above glycemic target (Matthews et al., 2019).
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