Victoza Clinical Trial Overview (LEADS 1-6, Rosenstock, and Pratley)

Question 1

If LEAD 1, 2, 3, 4, 5, 6, R, and P are written out, the information from many of the cards can be written below to form a table more easily memorized.

What were the background drugs for LEADS 1, 2, 3, 4, 5, 6, Rosenstock, Pratley?

Answer 1

BG: S, M, -, Mt, Ms, Ms, Md, ML = Background: SU, Metformin, None, Metformin/TZD, Metformin/SU, Metformin/Detemir, Metformin This is what defines the studies clinically with LEAD 1: add-on to SU, LEAD 2: add-on to met, LEAD 3: add-on to nothing or monotherapy, LEAD 4: add-on to met/TZD or dual sensitizer study, LEAD 5: add-on to met/SU, LEAD 6: add-on to met/SU, Rosenstock: add-on to met/detemir, and Pratley: add-on to met

Question 2

If LEAD 1, 2, 3, 4, 5, 6, R, and P are written out, the information from many of the cards can be written below to form a table more easily memorized.

What were the active comparators for LEADS 1, 2, 3, 4, 5, 6, Rosenstock, Pratley?

Answer 2

AC: T, S, S, -, G, E, D, Siti = Active Comparator: TZD, SU, SU, none, Glargine, Exenetide, none, Sitigliptin

Question 3

If LEAD 1, 2, 3, 4, 5, 6, R, and P are written out, the information from many of the cards can be written below to form a table more easily memorized.

Which was the only study in which the randomized component was greater than 26 weeks?

Answer 3

LEAD 3 (lira vs SU add-on to nothing; monotherapy); 52 weeks

Question 4

If LEAD 1, 2, 3, 4, 5, 6, R, and P are written out, the information from many of the cards can be written below to form a table more easily memorized.

Which studies in LEADS 1-5 (3a) had extensions and what were the extension durations?

Answer 4

LEAD 2 (lira vs SU add-on to met) had a 78 wk ext and LEAD 3 (lira vs SU add-on to nothing; monotherapy) had a 52 wk ext. For all of the trials: 0, 78, 52, 0, 0, 14, 52, 26 = LEAD 1: 0, LEAD 2: 78, LEAD 3: 52, LEAD 4: 0, LEAD 5: 0, LEAD 6: 14 (crossover exenitide to lira), ROSENSTOCK: 52, PRATLEY: 26.

Question 5

If LEAD 1, 2, 3, 4, 5, 6, R, and P are written out, the information from many of the cards can be written below to form a table more easily memorized.

Which studies of LEADS 1-6 including Pratley and Rosenstock had active comparators switched over to liraglutide in their extensions? What happened to A1c after the switch?

Answer 5

LEAD 6 (lira vs exenetide add-on to +/-met/SU) and Pratley (lira vs siti add-on to met) both switched and followed on lira 1.8 for 14 and 26 weeks respectively. Both had similar overall A1c reductions as those originally randomized to lira 1.8 mg. Pratley study had a 26 week extension of the origianl randomized and then a 26 week extension after switching the siti’s over to lira.

Question 6

If LEAD 1, 2, 3, 4, 5, 6, R, and P are written out, the information from many of the cards can be written below to form a table more easily memorized.

Which Victoza studies were open label?

Answer 6

LEAD 5 (lira vs glargine add-on to +/-met/SU), LEAD 6, Rosenstock (met/lira vs met/lira/detemir), Pratley (lira vs siti add-on to met)

Question 7

If LEAD 1, 2, 3, 4, 5, 6, R, and P are written out, the information from many of the cards can be written below to form a table more easily memorized.

Which studies had a lira 0.6 mg arm?

Answer 7

LEAD 1 (lira vs TZD add-on SU) and LEAD 2 (lira vs SU add-on to met)

Question 8

If LEAD 1, 2, 3, 4, 5, 6, R, and P are written out, the information from many of the cards can be written below to form a table more easily memorized.

In LEADS 1-5 (3a), which studies were not placebo controlled?

Answer 8

LEAD 3 (lira vs SU add-on to nothing; monotherapy). As an aside, Rosenstock (met/lira vs met/lira/detemir) and Pratley (lira vs siti add-on to met) were not placebo controlled.

Question 9

If LEAD 1, 2, 3, 4, 5, 6, R, and P are written out, the information from many of the cards can be written below to form a table more easily memorized.

In LEADS 1-5 (3a), which study was not double blinded?

Answer 9

LEAD 5 (lira vs glargine add-on to +/-met/SU)

Question 10

If LEAD 1, 2, 3, 4, 5, 6, R, and P are written out, the information from many of the cards can be written below to form a table more easily memorized.

Is weight loss with liraglutide likely due to central (brain) or peripheral (outside the CNS) action?

Answer 10

Likely peripheral action. Very little liraglutide gets into the CSF. Exenitide studies also support peripheral action.

Question 11

If LEAD 1, 2, 3, 4, 5, 6, R, and P are written out, the information from many of the cards can be written below to form a table more easily memorized.

In LEADS 1-5 (3a), what type of design is used: parallel, single group, crossover, or factorial?

Answer 11

Parallel

Question 12

If LEAD 1, 2, 3, 4, 5, 6, R, and P are written out, the information from many of the cards can be written below to form a table more easily memorized.

In LEADS 1-6, which two studies was liraglutide not superior in efficacy by A1c to active comparator arms?

Answer 12

LEAD 2 (lira vs SU add-on to metformin) where A1c change was similar and LEAD 4 (lira vs NO ACTIVE COMPARATOR add-on to met/TZD) since there was no active comparator.

Question 13

If LEAD 1, 2, 3, 4, 5, 6, R, and P are written out, the information from many of the cards can be written below to form a table more easily memorized.

In LEADS 1-6, which two studies had glimepiride as active comparators? Background? What were the doses?

Answer 13

ACTIVE COMPARATORS: LEAD 2 glimipiramide was 4 mg (Lira vs SU add-on to metformin) and LEAD 3 glimipiride was 8 mg (lira vs SU no background; monotherapy) which makes sense if you use Monotherapy you want Maximum dose (8mg). BACKGROUND: LEADS 1 (lira vs TZD add-on SU) AND 5 glimipiride was 2-4 mg. PEARL: The maximum allowable dose in most patients provides no additional glucose lowering effect than half the maximum dose.

Question 14

If LEAD 1, 2, 3, 4, 5, 6, R, and P are written out, the information from many of the cards can be written below to form a table more easily memorized.

In LEADS 1-6, which study had the most patients? Which was a close second?

Answer 14

LEADS 1 (lira vs TZD add-on SU) and LEAD 2 (lira vs SU add-on to metformin) both had the most arms (the 0.6mg arms as well as placebo arms). LEAD 2 had nearly 2K patients (n=1091), just 50 more than LEAD 1. LEAD three was the only one close at n=~750.

Question 15

If LEAD 1, 2, 3, 4, 5, 6, R, and P are written out, the information from many of the cards can be written below to form a table more easily memorized.

In LEADS 1-6, which was the smallest study?

Answer 15

LEAD 4 (lira vs placebo add-on to met/TZD). Only 3 arms and there was little risk using small numbers with an obvious outcome.

Question 16

If LEAD 1, 2, 3, 4, 5, 6, R, and P are written out, the information from many of the cards can be written below to form a table more easily memorized.

In LEADS 1-6, which studies tied for lowest baseline A1c? Which had the highest?

Answer 16

LEAD 5 (lira vs glargine add-on to met/SU) and LEAD 6 (lira vs exenetide add-on to +/-met/SU) both had HgA1c of 5.2%. Majority on 2 OADS so predictable. The study with the highest baseline A1c was LEAD 4 (lira vs placebo add-on to met/TZD) at 5.5% which was not predictable.

Question 17

If LEAD 1, 2, 3, 4, 5, 6, R, and P are written out, the information from many of the cards can be written below to form a table more easily memorized.

In LEADS 1-6, which study had the oldest patients with the longest duration of diabetes?

Answer 17

LEAD 5 (lira vs glargine add-on to met/SU) which makes sense as those going on insulin are usually at a later disease progression (although the age range in LEAD 1-6 is only 53-57.5 years old).

Question 18

If LEAD 1, 2, 3, 4, 5, 6, R, and P are written out, the information from many of the cards can be written below to form a table more easily memorized.

In LEADS 1-6, which study had the youngest patients with the shortest duration of diabetes?

Answer 18

LEAD 3 (lira vs SU add-on to nothing). This makes sense as the younger should be earlier in the disease progression and good candidates for monotherapy (although the age range in LEAD 1-6 is only 53-57.5 years old).

Question 19

If LEAD 1, 2, 3, 4, 5, 6, R, and P are written out, the information from many of the cards can be written below to form a table more easily memorized.

In LEADS 1-6, which was trial had the largest baseline BMI? Smallest?

Answer 19

LEAD 4 (lira vs placebo add-on to met/TZD). TZDs can cause edema (weight gain). LEAD 4 had the largest baseline BMI and A1c, but the smallest number of patients (n=533). LEAD 1 had the smallest BMI, but had the most patients with anti lira antibodies (9-13% of lira treated patients)

Question 20

If LEAD 1, 2, 3, 4, 5, 6, R, and P are written out, the information from many of the cards can be written below to form a table more easily memorized.

In LEAD 5, which arm had the most severe hypoglycemia events? How many patients?

Answer 20

LEAD 5 (lira vs glargine add-on to met/SU). 6 episodes in 5 patients in the liraglutide arm.

Question 21

If LEAD 1, 2, 3, 4, 5, 6, R, and P are written out, the information from many of the cards can be written below to form a table more easily memorized.

In LEAD 6, after switching over from exenitide to liraglutide in the 14 week extension, what happened the A1c and weight compared to the liraglutide 1.8 group?

Answer 21

The exenitide to lira 1.8 mg group lost more weight (1.1kg lower than the lira 1.8 to lira 1.8 mg) and the A1c lowered similar to the lira 1.8 mg arm.