Type 2 Diabetes Treatment: Type 2 Diabetes Treatment: Novel Therapies Novel Therapies GLP-1 Receptor GLP-1 Receptor Agonists/Analogs and DPP-4 Agonists/Analogs and DPP-4 Inhibitors Inhibitors Jaime A. Davidson, MD, FACP, MACE Clinical Professor of Medicine Division of Endocrinology Touchstone Diabetes Center The University of Texas Southwestern Medical Center Dallas, Texas
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Type 2 Diabetes Treatment: Novel Therapies GLP-1 Receptor Agonists/Analogs and DPP-4 Inhibitors Jaime A. Davidson, MD, FACP, MACE Clinical Professor of.
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Type 2 Diabetes Treatment: Type 2 Diabetes Treatment: Novel Therapies Novel Therapies
• Increase in active GLP-1 with sitagliptin compared with placebo– Placebo: active GLP-1 increases to ~7 pM at 2−3 h– Sitagliptin: active GLP-1 increases to ~15−20 pM and remains
higher than placebo for ~6 h
Herman GA, et al. J Clin Endocrinol Metab. 2006;91:4612-4619.
Abbreviation: OGTT, oral glucose tolerance test.
Linagliptin PharmacodynamicsEffect on GLP-1 and Glucagon
Rauch T, et al. Diabetes Ther. 2012;3:10.
Statistically significant differences in postprandial intact GLP-1 (increased) and glucagon (decreased) vs placebo after 4 weeks of treatment in T2DM patients
Change from baseline in intact GLP-1 AUEC0–2h: Linagliptin: 18.5 pmol/h/LPlacebo: 0.4 pmol/h/LP <.0001
Change from baseline in glucagon AUEC0–2h: Linagliptin: -17.4 pg/h/LPlacebo: 1.3 pg/h/LP = .0452
Therapeutic Effect of GLP-1 in T2DM
GLP-1 significantly increased
• Insulin (17.4 nmol x 1-1 x min)*
• C-peptide (228 nmol x 1-1 x min)*
GLP-1 significantly reduced
• Fasting plasma glucose (normal levels reached in all patients)
• Pancreatic glucagon secretion (-1418 pmol x 1-1 x min)
• Plasma nonesterified fatty acids (-26.3 mmol x 1-1 x min)
Nauck MA, et al. Diabetologia. 1993;36:741-744. Nauck MA, et al. Diabetologia. 1993;36:741-744.
10 patients with unsatisfactory control of T2DM received infusions of GLP-1 or placebo
*Decreased again after plasma glucose normalized.
GLP-1 Receptor Agonists and GLP-1 Receptor Agonists and DPP-4 InhibitorsDPP-4 Inhibitors
Effects on HbA1c, Glucose, and Insulin Levels
Exenatide Has Beneficial Effects on FPG and Insulin in T2DM
Kolterman OG, et al. J Clin Endocrinol Metab. 2003;88:3082-3089.
N = 13
Mea
n F
PG
(m
g/dL
)
Pea
k M
ean
Incr
emen
tal
Ser
um I
nsul
in (
µU
/mL)
Abbreviation: FPG, fasting plasma glucose.
Exenatide Has Beneficial Effects on Postprandial Glucose and Glucagon
in T2DM
N = 24. Kolterman OG, et al. J Clin Endocrinol Metab. 2003;88:3082-3089.
Exenatide 0.1 μg/kg Placebo
Postprandial glucose, day 5 (mean)
Baseline
180 min (nadir)
300 min
15.9 mg/dL
126.4 mg/dL
177.8 mg/dL
Baseline
120 min (peak)
300 min
170.3 mg/dL
289.0 mg/dL
175.5 mg/dL
Postprandial glucagon, day 5 (mean)
Baseline 98.9 pg/mL
<5%–6% change over 180 min
Baseline
60 min
180 min
94.9 pg/mL
173.9 pg/mL
122.7 pg/mL
Klonoff DC, et al. Curr Med Res Opin. 2008:24:275-286.
Exenatide at 3 Years of Therapy Provides Sustained Effects on HbA1c
• 217 patients randomized to placebo, 5 µg exenatide, or 10 µg exenatide during prior 30-week placebo-controlled studies were transitioned to open-label exenatide treatment
• All patients had a minimum of 3 years of exenatide exposure for this analysis
• By week 12, exenatide reduced HbA1c by 1.1%• Reduction in HbA1c was sustained throughout 156 weeks of
treatment– Change from baseline to week 156 = -1.0% (95% CI, -1.1 to -0.8);
Exenatide qwk Percent to Goal Compared to Sitagliptin or Pioglitazone
• Metformin background– A significantly greater percentage of patients achieved HbA1c
<7.0% and HbA1c ≤6.5% with exenatide qwk than with sitagliptin (P <.0001) or pioglitazone (P <.05)2
1. Russell-Jones D, et al. Diabetes Care. 2012;35:252-258. 2. Bergenstal RM, et al. Lancet. 2010;376:431-439.
Exenatide qwk1
(n = 248)Sitagliptin1
(n = 163)Pioglitazone1
(n = 163)
HbA1c <7.0% 63%* 43% 61%
HbA1c ≤6.5% 49%* 26% 42%
• Diet and exercise background
*P <.001 vs sitagliptin.
Overview of GLP-1 Receptor Agonist Safety Data
Abbreviation: SU, sulfonylurea.Monami M, et al. Eur J Endocrinol. 2009;160:909-917.
Event
Odds Ratio
(95% confidence interval) P Value
Hypoglycemia*† 2.92 (1.49, 5.75) .002
With SUs 4.62 (1.89, 11.21) .001
Without SUs 1.37 (0.72, 2.63) .34
Cardiovascular events 0.99 (0.52, 1.91) .98
Nausea 3.88 (2.79, 5.42) <.001
Exenatide BID 8.38 (4.27, 16.48) <.001
Liraglutide 3.48 (2.29, 5.28) <.001
Vomiting 4.23 (2.67, 6.13) <.001
Diarrhea 2.36 (1.67, 3.33) <.001
* Odds ratio based on analysis of exenatide bid trials.† Severe hypoglycemia reported for 19 patients in exenatide BID trials and 1 patient in liraglutide trials.
• Meta-analysis• Predominantly exenatide and liraglutide
– n = 5429 receiving GLP-1 receptor agonists– n = 3053 receiving active comparators or placebo
Current DPP-4 Inhibitors
Sitagliptin
Vildagliptin(approved outside United States)
Saxagliptin
Alogliptin
Linagliptin
Placebo-corrected change from baseline in HbA1c - Monotherapy
Comparative Efficacies of DPP-4s
-0.1
-0.3
-0.2
-0.4
-0.8
-0.5
-0.6
-0.7
-0.9
-1.0
-1.1
-1.2
ΔH
bA
1c
(%)
Alogliptin1
12.5 mg 25 mg
7.9% 7.9%
Linagliptin2
5 mg 5 mg
8.1% 8.0%
Saxagliptin3
5 mg 5 mg
7%-10% 8.0%
Sitagliptin4
100 mg 100 mg
8.0% 8.0%
Vildagliptin5
50 mg BID 50 mg
8.6% 8.4%
The current DPP-4s have comparative efficacy
1. DeFronzo R, et al. Diabetes Care 2008;31:2315-2317. 2. Linagliptin Prescribing Information. 3. Saxagliptin Prescribing Information. 4. Sitagliptin Prescribing Information. 5. Vildagliptin Summary of Product Characteristics.
-0.56-0.59 -0.6
-0.7
-0.4
-0.6 -0.6
-0.8
-0.5
-0.7
Alogliptin Phase III Trials: HbA1c Change from Baseline After 26 Weeks
Abbreviations: MET, metformin; PIO, pioglitazone; SU, sulfonylurea. *P <.001 vs control.1. DeFronzo RA, et al. Diabetes Care. 2008;31:2315-2317. 2. Pratley RE, et al. Diabetes Obes Metab.
2009;11:167-176. 3. Nauck MA, et al. Int J Clin Pract. 2009;63:46-55. 4. Pratley RE, et al. Curr Med Res Opin. 2009;25:2361-2371. 5. Rosenstock J, et al. Diabetes Obes Metab. 2009;11:1145-1152.
LS Mean Change HbA1c from Baseline (%)
Alogliptin monotherapy1 Add-on therapy
Baseline HbA1c: 8.0%
Linagliptin Significantly Reduced HbA1c After 24 Weeks in Patients on a Stable Insulin Dose
Full analysis set (last observation carried forward). Change-from-baseline HbA1c at Week 24 is the primary endpoint. *Model includes treatment, baseline HbA1c, renal function, concomitant OADs. †Sensitivity analyses (FAS OC and PPS) revealed similar results. Yki-Järvinen H, et al. Diabetes Care. 2013;36:3875-3881.
Baseline HbA1c (%): 8.29 8.31
HbA1c Reduction with Linagliptin in Elderly Patients Over 75 Years
• In a prespecified subgroup analysis, there was no significant interaction according to patient age group (P = .1000)
• The study had a high proportion of elderly patients– 65−74 years: 26.1% linagliptin, 28.7% placebo– ≥75 years: 5.5% linagliptin, 6.5% placebo
Yki-Järvinen H, et al. Diabetes Care. 2013;36:3875-3881.
• The difference in HbA1c reduction between linagliptin and placebo was maintained during a 52-week free insulin titration period starting at week 24 (out to week 76)
Linagliptin Reduced HbA1c After 24 Weeks (Primary Endpoint) and Maintained it in a 52-
Week Free Insulin Titration Period
Stable insulin doseBaseline to week 24
Free insulin dosestarting at week 24
Full analysis set (last observation carried forward). *Model includes treatment, baseline HbA1c, renal function, concomitant OADs. Yki-Järvinen H, et al. Diabetes Care. 2013;36:3875-3881.
Linagliptin Significantly Reduced FPG After 24 Weeks and Maintained it in 28-Week Free
Insulin Titration Period
Week 24 Week 52
Change in FPG from baseline
Placebo-adjusted change with linagliptin:
-10.81 mg/dL
Placebo: -5.41 mg/dL
Linagliptin: -3.60 mg/dL
Stable insulin dosebaseline to week 24
Free insulin dosestarting at week 24
Full analysis set (observed case set). Yki-Järvinen H, et al. Diabetes Care. 2013;36:3875-3881.
Insulin Dose Stabilized in 1st 24 Weeks and Increased in Both Groups in 2nd 28-Week Free-Titration Period,
but With Greater Extent in Placebo Group
Stable insulin doseBaseline to week 24
Free insulin dosestarting at week 24
Full analysis set, original analysis. Yki-Järvinen H, et al. Diabetes Care. 2013;36:3875-3881.
Safety Profile of Linagliptin Compared with Placebo After 52 Weeks
• The overall risk of adverse events (AEs) with linagliptin (n = 631) vs placebo (n = 630):– Patients with any AEs
■78.4% with linagliptin vs 81.4% with placebo
– Patients with investigator-defined drug-related AEs ■18.7% with linagliptin vs 22.2% with placebo
– Patients with AEs leading to discontinuation of trial drug■3.3% with linagliptin vs 4.4% with placebo
– Patients with serious AEs■13.8% with linagliptin vs 13.2% with placebo
Yki-Järvinen H, et al. Diabetes Care. 2013;36:3875-3881.
Linagliptin, When Added to Insulin, and Its Association with the Risk of Hypoglycemia
Treated set (all patients who were treated with at least 1 dose of study medication). Yki-Järvinen H, et al. Diabetes Care. 2013;36:3875-3881.
Week 24 Week 52
Improved glycemic control with linagliptin added to insulindoes not appear to increase the risk of hypoglycemia
Linagliptin Shows Rates of Hypoglycemia Similar to Placebo
The Majority of Hypoglycemia is Nonsevere
Investigator-defined hypoglycemia AEs at week 24 by category
All Hypoglycemia
AEs
Severe
Placebo Linagliptin
Yki-Järvinen H, et al. Diabetes Care. 2013;36:3875-3881.
DocumentedSymptomatic(≤72 mg/dL)
DocumentedSymptomatic(<54 mg/dL)
Study Summary: Linagliptin as Add-On to Insulin
Efficacy and safety of linagliptin as add-on therapy to insulin in type 2 diabetes•Linagliptin significantly reduced HbA1c after 24 weeks in patients on a stable insulin dose (placebo-corrected reduction after 24 weeks -0.65%)•The efficacy of linagliptin was reliable in different prespecified subgroups, such as
– Elderly patients age ≥75 years
– Different categories of renal function•HbA1c reductions were maintained over 52 weeks •Linagliptin significantly reduced fasting plasma glucose after 24 weeks and maintained it in 28-week free insulin titration period•Linagliptin has a safety profile comparable to placebo•Incidence of hypoglycemia with linagliptin was comparable to placebo
Yki-Järvinen H, et al. Diabetes Care. 2013;36:3875-3881.
Both Sitagliptin and Saxagliptin Produced Greatest Reductions in HbA1c in Patients
with High Baseline HbA1c
Pla
ceb
o-S
ub
trac
ted
Δ i
n H
bA
1c
(%)
fro
m B
asel
ine
to
We
ek 1
2
–1.2
–1.0
–0.8
–0.6
–0.4
–0.2
050 mg QD 100 mg QD
–1.15 –1.18
Hanefeld M, et al. Curr Med Res Opin. 2007;23:1329-1339. Rosenstock J, et al. Curr Med Res Opin. 2009;25:2401-2411
Open-Label Saxagliptin in 66 PatientsOpen-Label Saxagliptin in 66 Patientswith Baseline HbA1c >10% to ≤12%with Baseline HbA1c >10% to ≤12%
Δ H
bA
1c
fro
m B
ase
lin
e to
W
eek
24 (
%) –0.8
–0.6
–0.4
–0.2
010 mg QD
–1.87
–1.0
–1.2
–1.4
–1.6
–1.8
–2.0
Incretin-Based Therapy Improves Glycemic Control When Used in Combination
Abbreviation: TZD, thiazolidinedione.*Added to thiazolidinedione plus metformin.
1. Bergenstal RM, et al. Lancet. 2010;376:431-439. 2. DeFronzo RA, et al. Diabetes Care. 2005;28:1092-1100. 3. DeFronzo RA, et al. Diabetes Care. 2010;33:951-957. 4. Buse JB, et al. Diabetes Care. 2004;27:2628-2635. 5. Buse JB, et al. Lancet. 2009;374:39-47. 6. Zinman B, et al. Diabetes Care. 2009;32:1224-1230. 7. Marre M, et al. Diabet Med. 2009;26:268-278. 8. Pratley R, et al. ADA 2012. Abstract 1158-P. 9. Nauck MA, et al. Int J Clin Pract. 2009;63:46-55. 10. Pratley RE, et al. Curr Med Res Opin. 2009;25:2361-2371. 11. Pratley RE, et al. Diabetes Obes Metab. 2009;11:167-176. 12. Haak T, et al. Diabetes Obes Metab. 2012;14:565-574. 13. Taskinen MR, et al. Diabetes Obes Metab. 2011;13:65-74. 14. Gomis R, et al. Diabetes Obes Metab. 2011;13:653-661. 15. Lewin AJ, et al. Clin Ther. 2012;34:1909-1919.e15. 16. Williams-Herman D, et al. Curr Med Res Opin. 2009;25:569-583. 17. Charbonnel B, et al. Diabetes Care. 2006;29:2638-2643. 18. Nauck M, et al. Diabetes Care. 2009;32:84-90. 19. Derosa G, et al. Metabolism. 2010;59:887-895. 20. Rosenstock J, et al. Clin Ther. 2006;28:1556-1568. 21. Hermansen K, et al. Diabetes Obes Metab. 2007;9:733-745. 22. Jadzinsky M, et al. Diabetes Obes Metab. 2009;11:611-622. 23. DeFronzo RA, et al. Diabetes Care. 2009;32:1649-1655. 24. Hollander P, et al. J Clin Endocrinol Metab. 2009;94:4810-4819. 25. Chacra AR, et al. Int J Clin Pract. 2009;63:1395-1406.
With Metformin Initial Tx
Added to Metformin Added to TZD
Added to Sulfonylurea
Exenatide ✔1,2 ✔3 ✔4
Liraglutide ✔5 ✔6* ✔5,7
Alogliptin ✔8 ✔9 ✔10 ✔11
Linagliptin ✔12 ✔13 ✔14 ✔15
Sitagliptin ✔16 ✔17,18 ✔19,20 ✔21
Saxagliptin ✔22 ✔23 ✔24 ✔25
Exenatide qwk HbA1c Reduction Compared with Sitagliptin or Pioglitazone
LS Mean. ITT population.*P <.001 vs sitagliptin. †P <.0001 vs sitagliptin ‡P <.05 vs pioglitazone. 1. Russell-Jones D, et al. Diabetes Care. 2012;35:252-258. 2. Bergenstal RM, et al. Lancet. 2010;376:431-439.
8.6%8.5%
Diet and exercise background1 Metformin background2
8.5%Baseline : 8.5% 8.5%8.5%
Exenatide qwk(n = 248)
Exenatide qwk(n = 160)
Fasting Plasma Glucose Improvement Was Greater with Exenatide qwk and Pioglitazone
LS Mean. ITT population.*P <.05 exenatide qwk vs sitagliptin.1. Russell-Jones D, et al. Diabetes Care. 2012;35:252-258. 2. Bergenstal RM, et al. Lancet. 2010;376:431-439
Metformin background2Diet and exercise background1
Exenatide qwk(n = 248)
Exenatide qwk(n = 160)
GLP-1 Receptor Agonists and DPP-4 Inhibitors
Effects on Weight
Why Is Weight a Concern?
• Most patients with T2DM are overweight/obese• Some currently available therapies cause weight gain
– Secretagogues– Glitazones– Insulin
Klonoff DC, et al. Curr Med Res. 2008;24:275-286.
Exenatide Open-Label Extension Study Continuous Loss of Body Weight
Baseline 99.3 kg
Δ B
ody
Wei
ght f
rom
Bas
elin
e (k
g)
Δ B
ody
Wei
ght f
rom
Bas
elin
e to
W
eek
156
(kg)
Baseline BMI (kg/m2)
<30
Exenatide qwk Weight Reduction Compared with Sitagliptin or Pioglitazone
*P <.001 vs sitagliptin. †P <.001 vs pioglitazone. ‡P = .002 vs sitagliptin. §P <.0001 vs pioglitazone. 1. Russell-Jones D, et al. Diabetes Care. 2012;35:252-258. 2. Bergenstal RM, et al. Lancet. 2010;376:431-439.
Diet and exercise background1 Metformin background2
8987.5 88.7Baseline (kg) : 87 8886.1
Exenatide qwk(n = 160)
Exenatide qwk(n = 248)
Effect of Liraglutide vs Standard Therapy on Body Weight
*P = .0001 vs glimepiride; †P <.05 vs placebo; ‡P ≤.0001 vs placebo.Abbreviations: SU, sulfonylurea; TZD, thiazolidinedione. 1. Garber A, et al. Lancet. 2009;373:473-481. 2. Nauck M, et al. Diabetes Care. 2009;32:84-90. 3. Marre M, et al. Diabetic Med. 2009;26:268-278. 4. Zinman B, et al. Diabetes Care. 2009;32:1224-1230. 5. Russell-Jones D, et al. Diabetologia. 2009;52:2046-2055.
• Gastric emptying was slowed with liraglutide, mainly during the first postprandial hour
– Mean estimated acetaminophen AUC0-60 min ratios
■ 0.62 with liraglutide vs placebo (P <.001)
■ 0.67 with liraglutide vs glimepiride (P <.001)
– Mean estimated percentage of acetaminophen exposure during the first postprandial hour (AUC0-60 min/AUC0-300 min)
■ 30% less with liraglutide compared with placebo (P <.001)
■ 29% less with liraglutide compared with glimepiride (P <.001)
– Acetominophen Cmax
■ 20% lower with liraglutide compared with placebo (P ≤.006)
■ 15% lower with liraglutide compared with glimepiride (P ≤.006)
Horowitz M, et al. Diabetes Res Clin Pract. 2012;97:258-266.
Neutral Effect of DPP-4 Inhibitors on Body Weight
• Sitagliptin produced statistically significant (P <.05) decreases of 0.5–0.8 kg in body weight from baseline at week 12 at all doses1
– Not significantly different from weight loss seen with placebo (-0.5 kg)
• Saxagliptin reduced body weight by -0.1 to -1.2 kg at week 24 compared with baseline2
– Weight loss was -1.4 kg with placebo
• In a comparative trial, mean weight loss after 26 weeks was -0.96 kg with sitagliptin vs -3.38 kg with liraglutide 1.8 mg and -2.86 kg with liraglutide 1.2 mg3
• Linagliptin produced no significant difference in body weight from baseline4
– No significant difference in body weight from baseline with placebo
1. Hanefeld M, et al. Curr Res Med Opin. 2007;23:1329-1339. 2. Rosenstock J, et al. Curr Med Res Opin. 2009;25:2401-2411. 3. Pratley RE, et al. Lancet. 2010;375:1447-1456. 4. Del Prato S, et al. Diabetes Obes Metab. 2011;13:258-267.
Effect of Alogliptin Monotherapy on Body Weight at 26 Weeks
DeFronzo RA, et al. Diabetes Care. 2008;31:2315-2317.
Effect of Linagliptin on Body Weight When Added to Insulin
Week 24 Week 52
Yki-Järvinen H, et al. Diabetes Care. 2013;36:3875-3881.
GLP-1 Receptor Agonists and DPP-4 Inhibitors
Effects on Lipids
Exenatide Has Beneficial Effects on Lipids
Klonoff DC, et al. Curr Med Res Opin. 2008;24:275-286.
Adverse Effects of GLP-1 Agonists and DPP-4 Inhibitors
1. Klonoff DC, et al. Curr Med Res Opin. 2008;24:275-286. 2. Kolterman OG, et al. J Clin Endocrinol Metab. 2003;88: 3082-3089. 3. Garber A, et al. Lancet. 2009;373:473-481. 4. Exenatide QW Prescribing Information. 5. Alogliptin Prescribing Information. 6. Linagliptin Prescribing Information. 7. Hanefeld M, et al. Curr Med Res Opin. 2007;23:1329-1339. 8. Sitagliptin Prescribing Information. 9. Rosenstock J, et al. Curr Med Res Opin. 2009;25:2401-2411. 10. White WB, et al. N Engl J Med. 2013;369:1327-1335. 11. Scirica BM, et al. N Engl J Med. 2013 3;369:1317-1326.
• In the first long-term clinical trials (EXAMINE and SAVOR), there was no difference in the rate of pancreatitis between the active drug and placebo10,11
Summary
GLP-1 Agonists and DPP-4 Inhibitors
GLP-1 Analogs vs Placebo*†
DPP-4 Inhibitors vs Placebo*
Achieved HbA1c <7%(risk ratio)
4.19†
(3.17 to 5.53)
2.47
(2.14 to 2.84)
HbA1c reduction (weighted mean difference in change in HbA1c percentage)
-0.97%
(-1.13% to -0.81%)
-0.74%
(-0.85% to -0.62%)
FPG level, mg/dL (weighted mean difference in change from baseline)
-27
(-33 to -21)
-18
(-22 to -14)
Weight, kg(weighted mean difference in change from baseline)
-2.37
(-3.95 to -0.78)
0.48
(0.30 to 0.66)
Incretin-Based Therapy in T2DMMeta-analysis
Amori RE, et al. JAMA. 2007;298:194-206. Slide courtesy of Dr. Jaime A. Davidson.
*The values in parentheses represent 95% CIs.†This value represents only exenatide vs placebo.
• Meta-analysis– GLP-1 receptor agonists
■ 19 studies with exenatide BID, 7 studies with exenatide qwk, 11 studies with liraglutide
– DPP-4 inhibitors■ 5 studies with alogliptin, 9 studies with linagliptin, 7 studies with saxagliptin,
23 studies with sitagliptin, 6 studies with vildagliptin
GLP-1 Receptor Agonists DPP-4 Inhibitors
HbA1c -1.10% to -1.59% -0.60% to -1.06%
FPG (mg/dL) -20.90 to -32.79 -13.15 to -28.29
Weight (kg) -2.03 to -2.41 -0.16 to -0.64
Incretin-Based Therapy in T2DMMeta-analysis
Aroda VR, et al. Clin Ther. 2012;34:1247-1258.e22.
Mean Change from Baseline
Summary: DPP-4 Inhibitors and GLP-1 Receptor Agonists
CharacteristicDPP-4
Inhibitors
GLP-1 Receptor Agonists
Expected HbA1c decrease1,2 0.5%−1.0% 0.8%−1.9%
How administered1 Orally Injected
Weight effect1,2 Neutral Weight loss
Common adverse events1-3 Headache, infection Nausea, vomiting
*Greater effect for this class.Abbreviations: AACE, American Association of Clinical Endocrinologists; ADA, American Diabetes Association; EASD, European Association for the Study of Diabetes.
1. Inzucchi SE, et al. Diabetes Care. 2012;35:1364-1379. 2. Garber AJ, et al. Endocr Pract. 2013;19(suppl 2):1-48.3. Dicker D. Diabetes Care. 2011;34(suppl 2):S276-S278. 4. Garber AJ, et al. Endocr Pract. 2013;19:327-336.
Benefits and Advantages of Incretin-Based Therapies
GLP-1 analogs• Lower HbA1c
~0.8%-1.1% from baseline
• Promote satiety and weight loss
• Beneficial effects on lipids
• Beneficial effects on systolic blood pressure
DPP-4 inhibitors• Lower HbA1c
~0.4%–0.9% from baseline
• Weight neutral (do not promote weight gain)
• Once-daily oral therapy– vs once daily, twice daily,