Emerging utility of once-weekly exenatide in patients with type 2 diabetes

Figures & data

Table 1 The six pivotal studies comparing exenatide weekly to various comparators

Trial	Comparator	Duration	Design	Background therapy	N	Change in A1c vs comparator group, % (SE) (P)	Change in body weight vs comparator group, kg (SE) (P)
DURATION 1^Citation11	Exenatide 10 µg twice daily	30 weeks (plus open-ended extension phase)	Randomized open-label, noninferiority comparator	Diet and exercise, metformin, sulfonylurea, thiazolidinedione, or combination of two	295	−1.9 (0.1) vs −1.5 (0.1) (P=0.0023)	−3.7 (0.5) vs −3.6 (0.5) (P=0.89)
DURATION 2^Citation13	Sitagliptin 100 mg once daily, pioglitazone 45 mg once daily	26 weeks	Randomized, double-blind, double-dummy, comparator	Metformin	491	−1.55 (0.100) vs −0.92 (0.099) vs −1.23 (0.099) (vs sitagliptin P<0.0001; vs pioglitazone P=0.0165)	−2.31 (0.323) vs −0.77 (0.322) vs 2.79 (0.320) (vs sitagliptin P=0.0002; vs pioglitazone P<0.0001)
DURATION 3^Citation15	Insulin glargine	26 weeks (+58 week extension)	Randomized, open-label, comparator	Metformin ± sulfonylurea	456	−1.32 (0.07) vs −1.17 (0.08) (P=0.12)	−2.49 (0.28) vs +2.01 (0.28) (P<0.001)
DURATION 4^Citation14	Metformin 1,000–2,500 mg once daily, sitagliptin 100 mg daily, pioglitazone 45 mg daily	26 weeks	Randomized, double-blind, double-dummy comparator	Diet and exercise	820	−1.53 (0.07) vs −1.48 (0.07) vs −1.15 (0.08) vs −1.63 (0.08) (vs metformin P=0.62; vs sitagliptin P<0.001; vs pioglitazone P=0.328)	−2.0 (0.2) vs −2.0 (0.2) vs −0.8 (0.3) vs + 1.5 (0.3) (vs metformin P=0.892; vs sitagliptin P<0.001; vs pioglitazone P<0.001)
DURATION 5^Citation12	Exenatide 10 µg twice daily	24 weeks	Randomized, open-label, noninferiority, comparator	Diet and exercise, metformin, sulfonylurea, thiazolidinedione, or combination of two	252	−1.6 (0.1) vs −0.9 (0.1) (P<0.0001)	−2.33 (0.369) vs −1.37 (0.386) (P=0.0514)
DURATION 6^Citation34	Liraglutide 1.8 mg once daily	26 weeks	Randomized, open-label, comparator	Metformin, sulfonylurea ± thiazolidinedione	911	−1.28 (0.05) vs −1.48 (0.05) (P=0.002)	−2.68 (0.18) vs −3.6 (0.18) (P<0.001)

Abbreviations: DURATION, The Diabetes Therapy Utilization: Researching Changes in A_1c, Weight, and Other Factors Through Intervention With Exenatide Once Weekly; SE, standard error.

Table 2 Adverse events and withdrawal rates

Trial (once-weekly exenatide)	Comparator	Adverse events (%)				Withdrawal % due to adverse reaction
		Nausea	Vomiting	Injection reaction	Hypoglycemia
DURATION-1^Citation11	Exenatide LAR	26.4	10.8	22	5.4	6.1
	Exenatide	34.5	18.6	11.7	6.2	4.8
DURATION-2^Citation13	Exenatide LAR	24.0	11.0	10.0	1.0	6.3
	Sitagliptin	10.0	2.0	7.0	3.0	3.0
	Pioglitazone	5.0	3.0	7.0	1.0	3.6
DURATION-3^Citation15	Exenatide LAR	15.0	6.0	13.0	8.0	9.0
	Insulin glargine	2.0	3.0	2.0	26.0	2.0
DURATION-4^Citation14	Exenatide LAR	11.3	4.8	10.5	5.2	2.4
	Metformin	6.9	3.3	10.2	4.1	2.4
	Sitagliptin	3.7	1.8	6.7	3.1	0.6
	Pioglitazone	4.3	3.1	3.7	3.7	3.1
DURATION-5^Citation12	Exenatide LAR	14.0	4.7	5.4	3.9	5.0
	Exenatide bid	35.0	8.9	5.2	3.3	5.0
DURATION-6^Citation34	Exenatide LAR	9.3	3.7	10.0	10.8	2.6
	Liraglutide	20.4	10.7	1.0	8.9	5.3

Abbreviations: DURATION, The Diabetes Therapy Utilization: Researching Changes in A_1c, Weight, and Other Factors Through Intervention With Exenatide Once Weekly; LAR, long-acting release.

DruckerDJBuseJBTaylorKDURATION-1 Study GroupExenatide once weekly versus twice daily for the treatment of type 2 diabetes: a randomised, open-label, non-inferiority studyLancet200837296451240 125018782641

 PubMed Web of Science ®Google Scholar

BergenstalRMWyshamCMacconellLDURATION-2 Study GroupEfficacy and safety of exenatide once weekly versus sitagliptin or pioglitazone as an adjunct to metformin for treatment of type 2 diabetes (DURATION-2): a randomised trialLancet20103769739431 43920580422

 PubMed Web of Science ®Google Scholar

DiamantMVan GaalLGuerciBExenatide once weekly versus insulin glargine for type 2 diabetes (DURATION-3): 3-year results of an open-label randomised trialLancet Diabetes Endocrinol201426464 47324731672

 PubMed Web of Science ®Google Scholar

Russell-JonesDCuddihyRMHanefeldMDURATION-4 Study GroupEfficacy and safety of exenatide once weekly versus metformin, pioglitazone, and sitagliptin used as monotherapy in drug-naive patients with type 2 diabetes (DURATION-4): a 26-week double-blind studyDiabetes Care2012352252 25822210563

 PubMed Web of Science ®Google Scholar

BlevinsTPullmanJMalloyJDURATION-5: exenatide once weekly resulted in greater improvements in glycemic control compared with exenatide twice daily in patients with type 2 diabetesJ Clin Endocrinol Metab20119651301 131021307137

 PubMed Web of Science ®Google Scholar

PollackMFPurayidathilFWBolgeSCWilliamsSAPatient-reported tolerability issues with oral antidiabetic agents: associations with adherence; treatment satisfaction and health-related quality of lifeDiabetes Res Clin Pract2010872204 21020036433

 PubMed Web of Science ®Google Scholar