Patient considerations in type 2 diabetes – role of combination dapagliflozin–metformin XR

Figures & data

Figure 1 The organ systems involved in the pathogenesis of T2DM.

Notes: Reprinted from Trends in Pharmacological Sciences; 32(2); Bailey CJ; Renal glucose reabsorption inhibitors to treat diabetes; pages 63–71; Copyright 2011; with permission from Elsevier.⁷³
Abbreviations: AGI, α-glucosidase inhibitor; DPP-4i, dipeptidyl peptidase-4 inhibitor; GLP-1, glucagon-like peptide-1; SGLT2i, sodium–glucose cotransporter 2 inhibitor; SU, sulfonylurea; T2DM, type 2 diabetes mellitus; TZD, thiazolidinedione.

Table 1 Summary of placebo-controlled trials detailing efficacy of dapagliflozin monotherapy or combination with metformin

Reference	Intervention	Change in A1C from baseline (%)	Change in body weight from baseline (kg)	Change in systolic blood pressure from baseline (mmHg)
Bailey et al^Citation48	MET + placebo	−0.3	−0.9	−0.2
	MET + dapa 5 mg	−0.7	−3	−4.3
	MET + dapa 10 mg	−0.84	−2.9	−5.1
Bailey et al^Citation49	MET + placebo	0.02	1.4	1.5
	MET + dapa 5 mg	−0.58	−1.7	−1.1
	MET + dapa 10 mg	−0.78	−1.7	−0.3
Henry et al^Citation50	MET XR + placebo	−1.4	−1.3	−1.8
	Dapa 5 mg + placebo	−1.25	−2.6	−4.2
	MET XR + dapa 5 mg	−2.1	−2.7	−2.9
	MET XR + placebo	−1.4	−1.4	−1.2
	Dapa 10 mg + placebo	−1.5	−2.7	−4
	MET XR + dapa 10 mg	−2	−3.3	−3.3
Nauck et al^Citation51	MET + dapa	−0.52	−3.22	−4.3
	MET + glipizide	−0.52	1.44	0.8
Matthaei et al^Citation52	MET + SU + placebo	−0.17	−0.6	−0.3
	MET + SU + dapa 10 mg	−0.86	−2.7	−4
Jabbour et al^Citation53	Sitagliptin ± MET + placebo	0	−0.3	−5.1
	Sitagliptin ± MET + dapa 10 mg	−0.5	−2.1	−6
Ferrannini et al^Citation54	Placebo	−0.23	−2.2	−0.9
	Dapa 5 mg	−0.77	−2.8	−2.3
	Dapa 10 mg	−0.89	−3.2	−3.6

Abbreviations: dapa, dapagliflozin; MET, metformin; SU, sulfonylurea; XR, extended release.

Table 2 Case study physical examination and results of laboratory testsa

Physical examination	Laboratory tests
• Weight: 99.8 kg; height: 1.63 m; BMI: 37.8 kg/m^2	• FPG: 166 mg/dL (normal range: 65–109 mg/dL)
• Blood pressure: lying, right arm 142/80 mmHg; sitting, right arm 140/76 mmHg	• Creatinine: 1.0 mg/dL (normal range: 0.5–1.4 mg/dL)
• Pulse: 80 bpm; respirations 20 per minute	• Blood urea nitrogen: 16 mg/dL (normal range: 7–30 mg/dL)
• Eyes: corrective lenses, pupils equal and reactive to light and accommodation, Fundi clear, no arteriolovenous nicking, no retinopathy	• Sodium: 141 mg/dL (normal range: 135–146 mg/dL)
	• Potassium: 4.3 mg/dL (normal range: 3.5–5.3 mg/dL)
• Thyroid: nonpalpable	• Lipid panel
• Lungs: clear to auscultation	○ Total cholesterol: 180 mg/dL (normal: <200 mg/dL)
• Heart: rate and rhythm regular, no murmurs or gallops	○ HDL cholesterol: 52 mg/dL (normal: ≥40 mg/dL)
• Vascular assessment: no carotid bruits; femoral, popliteal, and dorsalis pedis pulses 2+ bilaterally	○ LDL cholesterol (calculated): 92 mg/dL (normal: <100 mg/dL)
	○ Triglycerides: 177 mg/dL (normal: <150 mg/dL)
	○ Cholesterol-to-HDL ratio: 3.5 (normal: <5)
	• AST: 14 IU/L (normal: 0–40 IU/L)
	• ALT: 19 IU/L (normal: 5–40 IU/L)
	• Alkaline phosphatase: 56 IU/L (normal: 35–125 IU/L)
	• A1c: 7.8% (normal: 4–6%)
	• Urine microalbumin: 20 mg (normal: <30 mg)

Note:

a Samples for the laboratory tests were drawn 5 days before the office visit.

Abbreviations: ALT, alanine aminotransferase; AST, aspartate aminotransferase; BMI, body mass index; FPG, fasting plasma glucose; A_1c, glycated hemoglobin; HDL, high-density lipoprotein; LDL, low-density lipoprotein.

Bailey CJ Renal glucose reabsorption inhibitors to treat diabetes Trends Pharmacol Sci 2011 32 2 63 71 21211857

 PubMed Web of Science ®Google Scholar

Bailey CJ Gross JL Peiters A Effect of dapagliflozin in patients with type 2 diabetes who have inadequate glycaemic control with metformin: a randomized, double-blind, placebo-controlled trial Lancet 2010 375 2223 2233 20609968

 PubMed Web of Science ®Google Scholar

Bailey CJ Gross JL Hennicken D Dapagliflozin add on to metformin in type 2 diabetes inadequately controlled with metformin: a randomized, double-blind, placebo-controlled 102 week trial BMC Med 2013 11 43 23425012

 PubMed Web of Science ®Google Scholar

Henry RR Murray AV Marmolejo MH Hennicken D Ptaszynska A List JF Dapagliflozin, metformin XR, or both: initial pharmacotherapy for type 2 diabetes, a randomised controlled trial Int J Clin Pract 2012 66 5 446 456 22413962

 PubMed Web of Science ®Google Scholar

Nauck MA Del Prato S Meier JJ Dapagliflozin versus glipizide as add-on therapy in patients with type 2 diabetes who have inadequate glycemic control with metformin: a randomized, 52-week, double-blind, active-controlled noninferiority trial Diabetes Care 2011 34 9 2015 2022 21816980

 PubMed Web of Science ®Google Scholar

Matthaei S Bowering K Rohwedder K Grohl A Parikh S Study 05 Group Dapagliflozin improves glycemic control and reduces body weight as add-on therapy to metformin plus sulfonylurea: a 24-week randomized, double-blind clinical trial Diabetes Care 2015 38 365 372 25592197

 PubMed Web of Science ®Google Scholar

Jabbour S Hardy E Sugg J Parikh S Study 10 Group Dapagliflozin is effective as add-on therapy to sitagliptin with or without metformin: a 24-week, multicenter, randomized, double-blind, placebo-controlled study Diabetes Care 2014 37 3 740 750 24144654

 PubMed Web of Science ®Google Scholar

Ferrannini E Ramos SJ Salsali A Tang W List JF Dapagliflozin monotherapy in type 2 diabetic patients with inadequate glycemic control by diet and exercise: a randomized, double-blind, placebo-controlled, phase 3 trial Diabetes Care 2010 33 10 2217 2224 20566676

 PubMed Web of Science ®Google Scholar