| 1. |
- DeFronzo, Ralph A., et al.
(författare)
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Type 2 diabetes mellitus
- 2015
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Ingår i: Nature Reviews Disease Primers. - : Springer Science and Business Media LLC. - 2056-676X. ; 1
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Tidskriftsartikel (refereegranskat)abstract
- Type 2 diabetes mellitus (T2DM) is an expanding global health problem, closely linked to the epidemic of obesity. Individuals with T2DM are at high risk for both microvascular complications (including retinopathy, nephropathy and neuropathy) and macrovascular complications (such as cardiovascular comorbidities), owing to hyperglycaemia and individual components of the insulin resistance (metabolic) syndrome. Environmental factors (for example, obesity, an unhealthy diet and physical inactivity) and genetic factors contribute to the multiple pathophysiological disturbances that are responsible for impaired glucose homeostasis in T2DM. Insulin resistance and impaired insulin secretion remain the core defects in T2DM, but at least six other pathophysiological abnormalities contribute to the dysregulation of glucose metabolism. The multiple pathogenetic disturbances present in T2DM dictate that multiple antidiabetic agents, used in combination, will be required to maintain normoglycaemia. The treatment must not only be effective and safe but also improve the quality of life. Several novel medications are in development, but the greatest need is for agents that enhance insulin sensitivity, halt the progressive pancreatic β-cell failure that is characteristic of T2DM and prevent or reverse the microvascular complications. For an illustrated summary of this Primer, visit: http://go.nature.com/V2eGfN.
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| 2. |
- Simonson, Donald C., et al.
(författare)
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Continuous Glucose Monitoring Profiles and Health Outcomes After Dapagliflozin Plus Saxagliptin vs Insulin Glargine
- 2024
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Ingår i: JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM. - 0021-972X .- 1945-7197.
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Tidskriftsartikel (refereegranskat)abstract
- Context: Glycemic variability and hypoglycemia during diabetes treatment may impact therapeutic effectiveness and safety, even when glycated hemoglobin (HbA1c) reduction is comparable between therapies. Objective: We employed masked continuous glucose monitoring (CGM) during a randomized trial of dapagliflozin plus saxagliptin (DAPA + SAXA) vs insulin glargine (INS) to compare glucose variability and patient-reported outcomes (PROs). Design: 24-week substudy of a randomized, open-label, 2-arm, parallel-group, phase 3b study. Setting: Multicenter study (112 centers in 11 countries). Patients: 283 adults with type 2 diabetes (T2D) inadequately controlled with metformin +/- sulfonylurea. Interventions: DAPA + SAXA vs INS. Main outcome measures: Changes in CGM profiles, HbA1c, and PROs. Results: Changes from baseline in HbA1c with DAPA + SAXA were similar to those observed with INS, with mean difference [95% confidence interval] between decreases of -0.12% [-0.37 to 0.12%], P = .33. CGM analytics were more favorable for DAPA + SAXA, including greater percent time in range (> 3.9 and <= 10 mmol/L; 34.3 +/- 1.9 vs 28.5 +/- 1.9%, P = .033), lower percent time with nocturnal hypoglycemia (area under the curve <= 3.9 mmol/L; 0.6 +/- 0.5 vs 2.7 +/- 0.5%, P = .007), and smaller mean amplitude of glycemic excursions (-0.7 +/- 0.1 vs -0.3 +/- 0.1 mmol/L, P = .017). Improvements in CGM were associated with greater satisfaction, better body weight image, less weight interference, and improved mental and emotional well-being. Conclusion: DAPA + SAXA and INS were equally effective in reducing HbA1c at 24 weeks, but people with T2D treated with DAPA + SAXA achieved greater time in range, greater reductions in glycemic excursions and variability, less time with hypoglycemia, and improved patient-reported health outcomes.
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| 3. |
- Jendle, Johan, 1963-, et al.
(författare)
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Continuous glucose monitoring in patients with type 2 diabetes treated with glucagon-like peptide-1 receptor agonist dulaglutide in combination with prandial insulin lispro : an AWARD-4 substudy
- 2016
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Ingår i: Diabetes, obesity and metabolism. - : Wiley-Blackwell Publishing Inc.. - 1462-8902 .- 1463-1326. ; 18:10, s. 999-1005
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Tidskriftsartikel (refereegranskat)abstract
- Background: Insulin use with GLP-1 receptor agonists is of interest because of the potential for glucose lowering with reduced insulin dosing versus an insulin-only regimen. The AWARD-4 trial, designed to compare these regimens, included a sub-study using 24-hour continuous glucose monitoring (CGM).Methods: The AWARD-4 trial randomised 884 conventional insulin regimens-treated patients to dulaglutide 1.5 mg, 0.75 mg and glargine, all in combination with prandial insulin lispro. The CGM sub-study included 144 patients inserted with Medtronic CGMS® iPro™ CGM device to enable 3-day glucose monitoring. CGM sessions were completed at weeks 0, 13, 26, and 52. CGM measures included mean 24-hour glucose, percentage time in target glucose ranges, hyper- and hypoglycaemia, and glucose variability. The primary objective was treatment comparison for percentage time CGM glucose in the 3.9-7.8 mmol/L range after 26 weeks.Results: At week 26, mean CGM glucose decreased in all treatment groups (change from baseline -2.8 ± 0.3, -2.4 ± 0.3, and -2.5 ± 0.3 mmol/L for dulaglutide 1.5 mg, 0.75 mg, and glargine, respectively); between-group differences were not statistically significant. Treatment groups were similar for percentage time in 3.9-7.8 mmol/L range. Percentage time in 3.9-10.0 mmol/L range was greater for dulaglutide 1.5 mg than glargine (p < 0.05). Dulaglutide and glargine were associated with decreased glucose variability for all CGM variability indices. Overall within-patient SD was significantly reduced with dulaglutide 1.5 mg versus glargine (p < 0.05). At week 52, there were no significant differences between groups for measures of normoglycaemia or near-normoglycaemia and for the overall within-patient SD. Treatment with glargine was associated with greater increases in percentage time glucose was ≤3.9 mmol/L with statistically significant differences between the groups at 52 weeks (p < 0.05).Conclusions: In combination with prandial lispro, treatment with dulaglutide and glargine resulted in similar proportions of glucose values in the normoglycaemic range, but dulaglutide provided an improved balance between the proportion of values within the near-normoglycaemia range and values within the hypoglycaemic range.
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