Table 2.
Summary of Clinical Data Evaluating the Effects of Parenteral Antidiabetes Agents on HbAlc, Weight, and Lipid Parameters in Patients with Type 2 Diabetes
| Agent | Study | Patient Population Randomized to Treatment Arm (n) |
Dosage | HbAlc, Percent Change From Baseline in Absolute Units |
Weight, kg Change From Baseline |
Lipids, Change From Baseline |
|---|---|---|---|---|---|---|
| Insulin Glargine |
Heine 200567 | 260 (uncontrolled by metformin plus sulfonylurea) |
Insulin glargine QD titrated to FBG < 5.6 mmol/L for 26 wk |
−1.11 | +1.8 | NR |
| Rosenstock 200657 |
104 (insulin-naïve; receiving sulfonylurea plus metformin) |
Insulin glargine 10 U/day titrated to FPG of 5.5–6.7 mmol/L for 24 wk |
−1.66 | +1.7 | (mg/dL) TC, -10.0; LDL-C, -2.0; HDL-C, no change; TG, -4I.0 |
|
| Barnett 200762 | 70 in insulin glargine/ exenatide group (receiving a single OAD) |
Insulin glargine QD titrated to FSG < 5.6 mmol/L for 16 wk (then crossover to exenatide) |
−1.36a | +1.0 in 1st period and +2.3 in 2nd period |
NR | |
| Fakhoury 200866 |
869 (uncontrolled by OAD) |
Insulin glargine 23–68 IU/day for 24 to 52 wk |
−0.76 to −2.36 | +2.57 to +3.7 | NR | |
| Insulin Aspart |
Nauck 200773 | 248 (receiving metformin plus a sulfonylurea) |
Biphasic insulin aspart 30/70 BID for 52 wk |
−0.89a | +2.9a | Greater increase in HDL-C with insulin aspart (LS mean, exenatide minus insulin, −0.04 mmol/L; P = 0.003; absolute values NR) |
| Insulin Detemir |
Fakhoury 200866 |
169 (uncontrolled by OAD) |
Insulin detemir mean dose of 37 IU/day for 20 wk |
−1.48 | +0.69 | NR |
| Pramlintide | Karl 200768 | 166 (uncontrolled by insulin) |
Pramlintide 120 µg BID or TID for 6 mo |
−0.56a | −2.8a | NR |
| Riddle 200774 | 105 (uncontrolled by insulin glargine with or without an OAD) |
Pramlintide 60 or l20 µg BID or TID for 16 wk |
−0.7a | −1.6a | NR | |
| Exenatide BID |
DeFronzo 200564 |
223 (receiving metformin) |
Exenatide 5–10 µg BID for 30 wk |
−0.40 to −0.78a | −1.6 to −2.8a | NR |
| Heine 200567 | 275 (uncontrolled by metformin plus a sulfonylurea) |
Exenatide 10 µg BID for 26 wk |
−l.11 | −2.3 | NR | |
| Kendall 200569 | 486 (receiving metformin plus a sulfonylurea) |
Exenatide 5–10 µg BID for 30 wk |
−0.55 to −0.77a | −1.6a | NR | |
| Barnett 200762 | 68 in exenatide/insulin glargine group (receiving a single OAD) |
Exenatide 10 µg BID for 16 wk (then crossover to insulin glargine) |
−1.36a | −2.0 in 1st period and −2.2 in 2nd period |
NR | |
| Nauck 200773 | 253 (receiving metformin plus a sulfonylurea) |
Exenatide 5 µg BID for 4 wk then 10 µg BID for 48 wk |
−1.04a | −2.5a | Greater increase in HDL-C with insulin aspart (LS mean, exenatide minus insulin, −0.04 mmol/L; P = 0.003; absolute values NR) |
|
| Zinman 200777 | 121 (uncontrolled by a thiazolidinedione with or without metformin) |
Exenatide 10 µg BID for 16 wk |
−0.89a | −1.75 | NR | |
| DeFronzo 200847 |
61 (receiving met- formin) |
Exenatide 5 µg BID for 1 wk then 10 µg BID for 1 wk (then crossover to sitagliptin) |
-15 (FPG, mg/dL) |
−0.8a | NR | |
| Drucker 200365 | 148 (uncontrolled by OAD with or without diet/exercise) |
Exenatide 10 µg BID for 30 wk |
−1.5a | −3.6 | (mmol/L) TC, −0.1; LDL-C, +0.03; HDL-C, −0.03; TG, −11% |
|
| Klonoff 200871 | 217 (uncontrolled by metformin with or without a sulfonyl urea) |
Exenatide 5 µg BID for 4 wk then 10 µg for up to 3.5 y |
−0.8a | −5.3a | (mg/dL) TC, −10.81a; LDL-C, −11.8a; HDL-C, +8.5a; TG, −44.1a |
|
| Exenatide Once Weeklyb |
Kim 200770 | 31 (uncontrolled by metformin with or without diet/exercise) |
Exenatide 0.8 to 2.0 mg/wk for 15 wk |
−1.4 to −1.7a | −3.8a (with 2.0 mg/wk dose) |
NR |
| Drucker 200865 (DURATION-1) |
147 (uncontrolled by OAD With or without diet/exercise) |
Exenatide 2 mg/wk for 30 wk |
−1.9a | −3.7 | (mmol/L) TC, −0.31; LDL-C, −0.13; HDL-C, −0.02; TG, −15% |
|
| Bergenstal 200863 |
120 (52-wk data of DURATION-I) |
Exenatide 2 mg/wk SC for 52 wk |
−2.0 | −4.1 | (mg/dL) TC, −7.9; LDL-C, −2.2; HDL-C, −0.3; TG, −40.1 |
|
| Liraglutideb | Vilsbøll 200776 | 123 (as monotherapy) | Liraglutide 0.65, 1.25, 1.90 mg QD SC for 14 wk |
−0.98 to −1.45 | −2.99 (1.90 mg dose) |
No consistent changes among treatment in TC, LDL-C, HDL-C (no data shown) |
| Seino 200875 | 180 (Japanese patients) |
Liraglutide 0.1−0.9 mg/day SC for 14 wk |
−0.72 to −1.67 | +0.13 to −0.48 | NR | |
| Garber 200948 (LEAD-3) |
498 (receiving an OAD plus diet/exercise) |
Liraglutide 1.2–1.8 mg/day for 52 wk |
−0.84 to −1.14 | −2.0 to −2.5a | NR | |
| Marre 200972 (LEAD-I) |
695 (added to sulfonylurea) |
Liraglutide 0.6, 1.2, 1.8 mg QD SC for 26 wk |
−1.1a | +0.7 to −0.2 | NR | |
| Nauck 200952 (LEAD-2) |
725 (plus metformin) | Liraglutide 0.6–1.8 mg/day for 26 wk |
−0.7 to −1.0a | −1.8 to −2.8a | NR | |
| Zinman 200978 (LEAD-4) |
356 (in combination with metformin and rosiglitazone) |
Liraglutide 1.2–1.8 mg/day for 26 wk |
−1.5 | −1.0 to −2.0 | (mmol/L) TC, −0.20 to −0.21; LDL-C, −0.23 to −0.28a; HDL-C, −0.03 to −0.04; TG, −0.32 to −0.38a |
a
P < 0.05.
b
Not currently approved by the US Food and Drug Administration; undergoing regulatory review.
Abbreviations: DURATION-1, Diabetes Therapy Utilization; Researching Changes in AIC, Weight and Other Factors Through Intervention with Exenatide Once Weekly-1; FBG, fasting blood glucose; FPG, fasting plasma glucose; FSG, fasting serum glucose; HDL-C, high-density lipoprotein cholesterol; LEAD, Liraglutide Effects and Actions in Diabetes; LDL-C, low-density lipoprotein cholesterol: LS, least squares: NR, not reported; OAD, oral antidiabetes (agent); SC, subcutaneous: TC, total cholesterol; TG, triglyceride.