Glycaemic, weight, and blood pressure changes associated with early versus later treatment intensification with dapagliflozin in United Kingdom primary care patients with type 2 diabetes mellitus

Wilding, John; Rigney, Una; Blak, Betina; Nolan, Stephen; Fenici, Peter; Medina, Jesús

doi:10.1016/j.diabres.2019.107791

Cited by 7 publications

(5 citation statements)

References 32 publications

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“…More profound weight loss observed in our study may be related to the poor baseline glycemic control in our cohort and multicombination antidiabetic drug therapy. Patients with poorer diabetes control are likely to have more profound glycosuria and the related negative energy balance from SGLT-2i as evidenced by previous studies with greater weight loss and better average HbA1c reduction as a consequence[ 18 - 20 ], supporting our observations. Although the systolic BP reduction following treatment did not reach statistical significance ( P = 0.08) possibly because of the low number of participants in our cohort, a tendency towards significance in this study supports the beneficial effects of dapagliflozin as shown by other studies[ 21 , 22 ].…”

Section: Discussionsupporting

confidence: 89%

Comparative efficacy of sodium glucose cotransporter-2 inhibitors in the management of type 2 diabetes mellitus: A real-world experience

Islam,

Jose,

Alkhalifah

et al. 2024

World J Diabetes

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BACKGROUND Sodium glucose cotransporter-2 inhibitors (SGLT-2i) are a class of drugs with modest antidiabetic efficacy, weight loss effect, and cardiovascular benefits as proven by multiple randomised controlled trials (RCTs). However, real-world data on the comparative efficacy and safety of individual SGLT-2i medications is sparse. AIM To study the comparative efficacy and safety of SGLT-2i using real-world clinical data. METHODS We evaluated the comparative efficacy data of 3 SGLT-2i drugs (dapagliflozin, canagliflozin, and empagliflozin) used for treating patients with type 2 diabetes mellitus. Data on the reduction of glycated hemoglobin (HbA1c), body weight, blood pressure (BP), urine albumin creatinine ratio (ACR), and adverse effects were recorded retrospectively. RESULTS Data from 467 patients with a median age of 64 (14.8) years, 294 (62.96%) males and 375 (80.5%) Caucasians were analysed. Median diabetes duration was 16.0 (9.0) years, and the duration of SGLT-2i use was 3.6 (2.1) years. SGLT-2i molecules used were dapagliflozin 10 mg (n = 227; 48.6%), canagliflozin 300 mg (n = 160; 34.3%), and empagliflozin 25 mg (n = 80; 17.1). Baseline median (interquartile range) HbA1c in mmol/mol were: dapagliflozin - 78.0 (25.3), canagliflozin - 80.0 (25.5), and empagliflozin - 75.0 (23.5) respectively. The respective median HbA1c reduction at 12 months and the latest review (just prior to the study) were: 66.5 (22.8) & 69.0 (24.0), 67.0 (16.3) & 66.0 (28.0), and 67.0 (22.5) & 66.5 (25.8) respectively (P < 0.001 for all comparisons from baseline). Significant improvements in body weight (in kilograms) from baseline to study end were noticed with dapagliflozin - 101 (29.5) to 92.2 (25.6), and canagliflozin 100 (28.3) to 95.3 (27.5) only. Significant reductions in median systolic and diastolic BP, from 144 (21) mmHg to 139 (23) mmHg; (P = 0.015), and from 82 (16) mmHg to 78 (19) mmHg; (P < 0.001) respectively were also observed. A significant reduction of microalbuminuria was observed with canagliflozin only [ACR 14.6 (42.6) at baseline to 8.9 (23.7) at the study end; P = 0.043]. Adverse effects of SGLT-2i were as follows: genital thrush and urinary infection - 20 (8.8%) & 17 (7.5%) with dapagliflozin; 9 (5.6%) & 5 (3.13%) with canagliflozin; and 4 (5%) & 4 (5%) with empagliflozin. Diabetic ketoacidosis was observed in 4 (1.8%) with dapagliflozin and 1 (0.63%) with canagliflozin. CONCLUSION Treatment of patients with SGLT-2i is associated with statistically significant reductions in HbA1c, body weight, and better than those reported in RCTs, with low side effect profiles. A review of large-scale real-world data is needed to inform better clinical practice decision making.

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Section: Discussionsupporting

confidence: 89%

Comparative efficacy of sodium glucose cotransporter-2 inhibitors in the management of type 2 diabetes mellitus: A real-world experience

Islam,

Jose,

Alkhalifah

et al. 2024

World J Diabetes

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“…[23] Similarly, a large-scale retrospective study from the UK found that early intensification of glucose-lowering therapy after an HbA 1c level of at least 7•0% (53 mmol/mol) was associated with an increased likelihood of, and a decreased time to, reaching an HbA 1c level less than 7•0% (53 mmol/mol), independent of first-line glucose-lowering medication. [16] As may be expected on the basis of similar findings from prior studies carried out in the UK and Germany, [24,25] patients who intensified therapy with a higher baseline HbA 1c achieved a greater absolute reduction in HbA 1c than those who intensified early. Despite this, mean HbA 1c levels were consistently lower in the early-intensification group, and the association of early intensification and increased likelihood of having an HbA 1c level less than 7•0% (53 mmol/mol) was observed at all time points.…”

Section: Discussionsupporting

confidence: 58%

Early versus late intensification of glucose-lowering therapy in patients with type 2 diabetes: Results from the DISCOVER study

Bonnet²,

Chen³

et al. 2021

Diabetes Research and Clinical Practice

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“…Despite the remarkable efficacy of dapagliflozin, the oncologist stopped this treatment after 3 kg of weight loss, even though it was difficult to determine if the advanced cancer or side-effects of the medications used, including alpelisib, were the cause. In two recent studies, mean weight loss under dapagliflozin was between 2.2 and 3.2 kg [ 15 ] and between -3.31 and -4.06% from baseline [ 16 ].…”

Section: Discussionmentioning

confidence: 99%

SGLT2 inhibitors as potentially helpful drugs in PI3K inhibitor-induced diabetes: a case report

Sahakian

Cattieuw

Ramillon-Cury

et al. 2021

Clin Diabetes Endocrinol

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Background Hyperglycemia is the most common side-effect of phosphatidylinositol 3-kinase (PI3K) inhibitors that are approved for the treatment of some advanced or metastatic breast cancers. This side-effect is likely due to the central role of PI3K in insulin signalling. Here we report the use of a sodium-glucose cotransporter 2 (SGLT2) inhibitor to manage severe hyperglycemia. Case presentation We describe a 74-year-old woman who developed severe uncontrolled hyperglycemia after commencing alpelisib, a new oral PI3K inhibitor indicated for a metastatic breast cancer, despite taking oral anti-diabetic drugs, metformin and vildagliptin, combined with intravenous insulin infusion of up to 250 units/day. The introduction of the SGLT2 inhibitor dapagliflozin rapidly improved blood glucose with a drastic reduction in insulin dosage, from 250 to 12 units/day, and without significant side-effects. Conclusions We report the successful management of hyperglycemia induced by alpelisib using a SGLT2 inhibitor without the need to discontinue effective cancer treatment.

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Glycaemic, weight, and blood pressure changes associated with early versus later treatment intensification with dapagliflozin in United Kingdom primary care patients with type 2 diabetes mellitus

Cited by 7 publications

References 32 publications

Comparative efficacy of sodium glucose cotransporter-2 inhibitors in the management of type 2 diabetes mellitus: A real-world experience

Comparative efficacy of sodium glucose cotransporter-2 inhibitors in the management of type 2 diabetes mellitus: A real-world experience

Early versus late intensification of glucose-lowering therapy in patients with type 2 diabetes: Results from the DISCOVER study

SGLT2 inhibitors as potentially helpful drugs in PI3K inhibitor-induced diabetes: a case report

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