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Insulin: Dosing Regimen and Adverse Effects01:16

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Insulin-replacement therapy usually includes both long-acting insulin (basal) and short-acting insulin (to cater to postprandial needs). In a diverse group of type 1 diabetes patients, the average daily insulin dose is typically 0.5-0.7 units/kg body weight. However, obese patients and pubertal adolescents may need more due to insulin resistance.
The basal dose constitutes about 40%-50% of the total daily dose, with the rest as premeal insulin. The mealtime insulin dose should mirror...
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Diabetes Mellitus: Overview and Type I Subtype01:22

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Diabetes mellitus is a chronic metabolic disorder characterized by high blood glucose levels due to inadequate insulin production, insulin resistance, or both. The condition affects millions worldwide and can significantly impact their health and quality of life.
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Insulin preparations are categorized by their duration of action into short-acting and long-acting types. Two strategies are used to modify insulin's absorption and pharmacokinetic profile: slowing the absorption post-subcutaneous injection, or altering human insulin's amino acid sequence or protein structure. These changes retain the insulin's ability to bind to the insulin receptor, but alter its behavior in solution or after injection.
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Incretins include glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), which stimulate insulin secretion post-meals. In type 2 diabetes, GIP's efficacy is reduced, making GLP-1 a viable drug target. GIP originates from preproGIP.
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Diabetes: Management and Pharmacotherapy01:15

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The therapy for diabetes aims to alleviate hyperglycemia-related symptoms, prevent acute metabolic decompensation, and reduce chronic end-organ complications. Glycemic control is evaluated through short-term (self-monitoring, continuous glucose monitoring) and long-term (A1c, fructosamine) metrics, enabling near real-time tracking of blood glucose levels and reflecting glycemic control over specific time frames.
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Type 2 diabetes, characterized by insulin resistance, arises when the insulin receptors on cells lose responsiveness to insulin, diminishing the cell's capacity to take up glucose, resulting in elevated blood glucose levels. To receive a diagnosis of Type 2 diabetes, a series of blood glucose tests are necessary to assess whether the blood glucose falls within normal parameters. If the result is out of the normal range, a patient may be diagnosed as prediabetic or diabetic, depending on the...
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Automated Insulin Delivery with SGLT2i Combination Therapy in Type 1 Diabetes.

Jose Garcia-Tirado1, Leon Farhy1,2, Ralf Nass2

  • 1Center for Diabetes Technology, University of Virginia, Charlottesville, Virginia, USA.

Diabetes Technology & Therapeutics
|March 7, 2022
PubMed
Summary

Adding empagliflozin to insulin therapy significantly improved glucose control in type 1 diabetes (T1D) patients using automated insulin delivery or predictive low glucose suspend systems. This combination therapy showed increased time-in-range without raising hypoglycemia risk, but ketoacidosis remains a concern.

Keywords:
Automated insulin infusionFree-living conditionsSodium-glucose cotransporter 2 inhibitorType 1 diabetes

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Area of Science:

  • Endocrinology
  • Metabolic Diseases
  • Pharmacology

Background:

  • Sodium-glucose cotransporter 2 inhibitors (SGLT2i) are used as adjunct therapy in type 1 diabetes (T1D).
  • Previous studies explored SGLT2i with insulin, but data combining low-dose SGLT2i with commercial automated insulin delivery (AID) or predictive low glucose suspend (PLGS) systems in free-living conditions is limited.

Purpose of the Study:

  • To evaluate the efficacy and safety of low-dose empagliflozin (EMPA) as an adjunct to insulin therapy in adults with T1D using commercial AID or PLGS systems.
  • To assess the impact of EMPA on glucose control, specifically time-in-range (TIR), in a real-world setting.

Main Methods:

  • An 8-week, randomized, controlled crossover trial involving adults with T1D.
  • Participants received either 5 mg/day empagliflozin (EMPA) or no drug (NOEMPA) adjunct to insulin.
  • Sequential use of AID (Control-IQ) and PLGS (Basal-IQ) systems for 4 and 2 weeks, respectively.
  • Primary endpoint: daytime TIR (70-180 mg/dL) while on AID.

Main Results:

  • On AID, EMPA significantly increased daytime TIR compared to NOEMPA (81% vs. 71%, p=0.04).
  • On PLGS, EMPA also significantly improved daytime TIR versus NOEMPA (80% vs. 63%, p<0.001).
  • No increased risk of hypoglycemia was observed, but one case of diabetic ketoacidosis occurred in a subject on SGLT2i and AID.

Conclusions:

  • Adjunct therapy with 5 mg daily empagliflozin significantly improves daytime glucose control in individuals with T1D using AID or PLGS systems.
  • The combination therapy does not appear to increase hypoglycemia risk.
  • The risk of ketosis and ketoacidosis necessitates modifications to closed-loop control algorithms for future SGLT2i studies in T1D.