Optimizing treatment strategies with insulin glargine in Type 2 diabetes

Figures & data

Figure 1. Insulin glargine molecular structure.

Figure 2. Bioavailability and bioactivity of basal insulins.

(A) Residual radioactivity at the injection site after injection of NPH insulin or glargine. (B) Plasma (free) concentrations and (C) glucose infusion rates after sc. injection of ultralente insulin, NPH insulin, glargine and CSII.

CSII: Continuous subcutaneous insulin infusion; NPH: Neutral protamine Hagedorn; sc.: Subcutaneous; SE: Standard error.

Panel (A) is reprinted with permission from [8]. © 2000 American Diabetes Association.

Panels (B) and (C) are reprinted with permission from [4]. © 2000 American Diabetes Association.

Figure 3. An algorithm for the initiation and intensification of insulin therapy in Type 2 diabetes.

FPG: Fasting plasma glucose; HBA_1c: Glycosylated hemoglobin; NPH: Neutral protamine Hagedorn insulin; PPG: Postprandial plasma glucose.

Adapted with permission from [22]. © 2009 American Diabetes Association.

Figure 4. Associations between end-of-study HbA_1c and rates of hypoglycemia (confirmed by blood glucose <3.6 mmol/l) during treatment with either NPH insulin or glargine in people with Type 2 diabetes (p = 0.021 between treatments).

HbA_1c: Glycosylated hemoglobin; NPH: Neutral protamine Hagedorn.

Reproduced with permission from [35]. © 2007 Elsevier, Inc.

Figure 5. Eight-point blood glucose profiles.

Effects of insulinization with once-daily glargine or three-times-daily lispro. *p < 0.0001; **p = 0.0041; ***p = 0.0137.

Reproduced with permission from [45]. © 2008 Elsevier, Inc.

Figure 6. Eight-point blood glucose profiles. Effects of adding one dose of glulisine to ongoing glargine.

*p < 0.05; **p < 0.0001.

Reprinted with permission from [50] © 2009 Blackwell Publishing Ltd.

Figure 7. Eight-point blood glucose profiles.

Effects of adding multiple doses of glulisine to ongoing glargine.

*p < 0.005; **p = 0.0003; ***p < 0.0001.

Reprinted with permission from [50]. © 2008 The Authors Journal Compilation and Blackwell Publishing Ltd.

Table 1. Overview of studies comparing insulin detemir and insulin glargine.

Study (year)	Study design	Intervention	Number (n) and % of patients at study completion	EOS mean HbA1c, % (mean change)	Mean baseline weight, kg (mean change)	EOS mean FPG, mmol/l (mean change)	EOS % of patients experiencing major hypoglycemic events	Ref.
Hollander et al. (2008)	Multinational, 52-week, open-label, parallel-group, noninferiority, treat-to target trial. Patients with a diagnosis of T2DM for ≥12 months who had been receiving an OAD or insulin, with or without OADs, for >4 months were randomized in a 2:1 ratio to receive detemir or glargine. Doses of insulin were titrated to achieve a prebreakfast (and predinner for detemir if required b.i.d.) plasma glucose target of ≤6.0 mmol/l	I: Insulin detemir once or twice daily + insulin aspart at mealtimeC: Insulin glargine once daily + insulin aspart at mealtimeInsulin detemir: 92 (43.0%) patients used once daily and 122 (57.0%) twice daily	I: 173 (80.1%)C: 84 (78.5%)Total: 257	Detemir: 7.19 (-1.52)Glargine: 7.03 (-1.68)	Detemir: 93.3 (+2.8)Glargine: 91.5 (+3.8)	Detemir: 7.05 (-2.56)Glargine: 6.68 (-2.92)	Detemir: 4.7%Glargine: 5.7%	[21]
Raskin et al. (2009)	Multicenter, randomized, open-label, parallel-group, treat-to-target trial with a 26-week treatment period comparing the efficacy and safety of detemir to glargine with insulin aspart in a basal-bolus regimen in patients with T2DM. Patients who had previously received any OAD, insulin or insulin plus OAD treatment regimens were randomized 2:1 to detemir or glargine	I: insulin detemir once or twice daily + insulin aspart at mealtimeC: insulin glargine once daily + insulin aspart at mealtimeInsulin detemir: 222 (87.4%) patients used once daily and 32 (12.6%) twice daily	I: 208 (82.0%)C: 113 (86.3%)Total: 321	Detemir: 7.13 (-1.08)Glargine: 6.92 (-1.28)	Detemir: 94.4 (+1.2)Glargine: 97.8 (+2.7)	Detemir: 7.21 (-2.4)Glargine: 7.46 (-2.15)	Detemir: 3.9%Glargine: 3.8%	[93]
Rosenstock et al. (2008)	Multinational, 52-week, randomized, open-label, parallel-group, noninferiority trial compared clinical outcomes following supplementation of oral glucose-lowering drugs with basal insulin analogs detemir and glargine in patients with T2DM. Doses of insulin were titrated to achieve a prebreakfast (and predinner for detemir if required b.i.d.) plasma glucose target of ≤6.0 mmol/l	I: insulin detemir once or twice dailyC: insulin glargine once dailyInsulin detemir: 104 (45.0%) patients used once daily and 127 (55.0%) twice daily	I: 291 (100%)C: 291 (100%)Total: 582	Detemir: 7.16 (-1.5)Glargine: 7.12 (-1.5)	Detemir: 87.4 (+3.0)Glargine: 87.4 (+3.9)	Detemir: 7.21 (-2.40)Glargine: 7.46 (-2.15)	Detemir: 2.0%Glargine: 3.0%	[18]
Swinnen et al. (2010)	Multinational, open-label design. Insulin-naive subjects with T2DM treated for ≥3 months with stable OADs (including metformin ≥1 g/day) and with HbA1c of 7.0–10.5% were included. Patients were randomized to 24-week treatment with glargine in the evening or detemir at breakfast and dinner. Glargine doses were increased every 2 days by two units until FPG reached <5.6 mmol/l, while the systematic titration of detemir involved three steps to obtain both fasting and predinner PG of <5.6 mmol/l	I: insulin detemir twice dailyC: insulin glargine once daily	I: 437 (89.9%)C: 456 (95.4%)Total: 893	Detemir: 7.24 (-1.46)Glargine: 7.16 (-1.54)	Detemir: 84.8 (+0.6)Glargine: 83.0 (+1.4)	Data not available	Detemir: 2.5%Glargine: 2.9%	[94]

b.i.d.: Twice daily; C: Control; EOS: End of study; FPG: Fasting plasma glucose; I: Intervention; OAD: Oral antidiabetic drug; PG: Plasma glucose; T2DM: Type 2 diabetes mellitus.

Adapted with permission from [44]. © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

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