Our Products > Drugs >Amaryl®


 

For Abridged prescription information please go to download center.

Amaryl® has a dual mode of action

amaryl

Sonnenberg GE et al. Ann Pharmacother 1997; 31: 671-676.
Weitgasser R et al. Diabetes Res Clin Pract 2003; 61: 13-19.

Comparison of OADs: action on insulin secretion and on insulin resistance

  Action on insulin
secretion
Action on insulin
resistance

Amaryl®

+

+

Conventional
Sulfonylureas

+

-

Glinides

+

-

Biguanides

-

+

Glitazones

-

+

a-Glucosidase Inhibitors

-

+

Henry RR. Endocrinol Metab Clin North Am 1997; 26: 553-573. Gitlin N, et al. Ann Intern Med 1998; 129: 36-38.
Neuschwander-Tetri BA, et al. Ann Intern Med 1998; 129: 38-41. Goldberg RB, et al. Diabetes Care 1998; 21: 1897-1903.
Fonseca V, et al. J Clin Endocrinol Metab 1998; 83: 3169-3176. Bell PM & Hadden DR. Endocrinol Metab Clin 1997; 26: 523-537.
DeFronzo RA, et al. N Engl J Med 1995; 333: 541-549. SinclairEM & Drucker DJ. Physiology 2005;20: 357-365. Hinnen D, et al. J Am Board Fam Med 2006;19: 612-620.

In vitro studies of Amaryl® and their significance for its in vivo action

  • Amaryl® associates with the Sulfonylurea receptor 2.5 - 3 times faster than Glibenclamide.1
  • Amaryl® dissociates from its binding protein 8-9 times faster than Glibenclamide.1
  • The amount of insulin released from human islets after Amaryl® treatment is drug dose-dependent.2
  • The amount of insulin released from human islets after Amaryl® treatment is glucose concentration dependent.2

Amaryl® augments first and second phase of insulin secretion3

  • Amaryl®: Treats both fasting and postprandial hyperglycaemia

First and second phase insulin secretion before and after treatment with Amaryl®

Amaryl-02

Amaryl® achieves greater reductions in glucose than placebo4

 

Change from baseline in FPG, 2-Hour PPG and HbA1c

Amaryl-04

  • Amaryl® decreased FPG by 46 mg/dL more than placebo (p<0.001).
  • Amaryl® decreased PPG by 72 mg/dL more than placebo (p<0.001).
  • Amaryl® decreased HbA1c by 1.4% more than placebo (p<0.001).

Amaryl® has proven extrapancreatic action on insulin resistance5

Amaryl-05

 

  • Significant reduction in HOMA-IR, an increase in MCR-g, and a reduction in HbA1c without changing extrapancreatic beta-cell function and urine CPR found with Amaryl®.
  • Increased plasma Adiponectin and decreased plasma TNF-alpha may underlie the improvement of insulin resistance with Glimepiride.

Comparison of Amaryl® with other drugs

  • Amaryl® has similar effect on HbA1c and FPG vs. Glibenclamide6
  • Amaryl® and Metformin are equally effective at lowering blood glucose7
  • Amaryl® is at least as effective as Gliclazide MR8 (Glimepiride reduced HbA1c from 8.2% to 7.2% & gliclazide 8.4% to 7.2%)

Amaryl® stimulates physiological insulin release in response to meals16

Amaryl-06

  • Amaryl® once daily stimulates insulin production primarily after meals when plasma glucose concentrations are highest, and controls blood glucose throughout the day.

In vitro evidence of extrapancreatic effect of Amaryl®17

  • Rate limiting step for glucose utilisation is glucose uptake via GLUT4 transporter
  • Amaryl® ↑ translocation of GLUT4 transporters from low-density microsomes to plasma membrane of insulin-resistant fat and muscle cells
  • Amaryl® appears to ↑ peripheral glucose uptake and to mimic the action of insulin

Amaryl-07

 

Comparison of extrapancreatic action of Amaryl® and other Sulfonylureas18

  • Amaryl® has better extrapancreatic activity compared to other Sulphonylureas (Glimepiride more than glibenclamide, gliclazide & glipizide)

Mean increase in plasma insulin (PI) and mean % decrease in blood glucose (BG) over 6 hours after single dose

Amaryl-08

 

Increase of peripheral insulin sensitivity: equivalent glucose control with less insulin secretion19

Amaryl-09

  • Amaryl® induces blood sugar decrease with lower insulin release than antidiabetic Sulfonylurea drugs.
  • This is a consequence of Amaryl®'s insulin sensitisation effect at peripheral tissues, which improves the underlying problem of insulin resistance.

Summary of Amaryl® efficacy

  • Amaryl® reduces hyperglycaemia by increasing insulin secretion and improving insulin resistance.
  • The binding property of Amaryl® to the ß-cell sulfonylurea receptor account for its higher blood sugar lowering efficacy, while its glucose level-dependent insulinotropic action might explain its lower incidence of hypoglycaemia compared with other Sulfonylureas.
  • The ability to augment the first-phase of insulin secretion makes Amaryl® unique.
  • In in vitro studies, Amaryl®'s extrapancreatic effect is evident from increased peripheral glucose uptake.
  • In in vivo studies, Amaryl® has shown better extrapancreatic activity compared to other Sulfonylureas. It induces blood sugar decrease with lower insulin release than other Sulfonylurea drugs.

Safety in special populations

  • No special risk in elderly, hepatic and renal impairment
    • ­ Plasma elimination with decreasing kidney function explainable on the basis of altered
      protein binding with an ­ in unbound drug 20
    • Safety in elderly (65-85 yrs old T2DM patients) similar to Glibenclamide 21
  • No intrinsic difference in oral clearance of glimepiride in obese patients compared with non-obese patients. No special dose consideration required for the use of Glimepiride in the treatment of obese patients with Type 2 diabetes.22

Cardiovascular safety: coronary artery disease23


Amaryl® reduces ischaemia during angioplasty in patients with coronary artery disease

Amaryl-10

 

Cardiovascular safety: ischaemic preconditioning24

  • Amaryl® maintains and Glibenclamide blunts the anti-anginal effect of ischaemic preconditioning

Mean (SD) chest pain scores during angioplasty

Non-diabetic group
Diabetic group
Control (n=7)
Glib (n=6)
Amaryl® (n=7)
Glib (n=6)
Amaryl® (n=5)
Glib + Nic(n=6)
Amaryl® + Nic(n= 6)
Inflation 1
5.9 ± 0.9
5.2 ± 1.5
6.2 ± 0.8
5.8 ± 0.8
6.2 ± 0.8
3.2 ± 0.8
4.4 ± 1.5
Inflation 2
2.4 ± 0.5*
5.3 ± 1.5
3.2 ± 0.8*
5.5 ± 1.5
3.4 ± 0.9*
2.7 ± 0.8
4.0 ± 1.2

*p<0.05 vs. inflation 1 within same group. † p<0.05 vs. Glib group alone at same time.
Glib = Glibenclamide; Nic = Nicorandil.
Myocardial responses were assessed following coronary angioplasty in diabetic and non-diabetic subjects receiving Amaryl® (2 mg or usual dose) or Glibenclamide (10 mg or usual dose).

 

Cardiovascular safety: myocardial infarction25


Antidiabetic treatment is associated with a better post-MI prognosis than no treatment

Amaryl-11

The 28-day mortality was analysed using a logistic model with Sulphonylurea, Metformin and insulin as
covariates. In this model, each odds ratio was adjusted for the prescription of the other antidiabetic drugs,
patients receiving several antidiabetic drugs being taken into account in this model.

Summary of cardiovascular safety of Amaryl®

  • Glimepiride appears to improve insulin resistance and atherosclerotic disorders.26
  • Amaryl® had a significantly lower blood pressure than Glibenclamide in endotoxin-shock rats.27

Safety: hypoglycaemia

  • Few episodes of severe hypoglycaemia with Amaryl® vs. Glibenclamide (6 vs. 38 episodes).29
  • Amaryl associated with fewer episodes of severe hypoglycemia than glibenclamide in routine clinical practice (0.86/ 1000 patient years vs 5.6 / 1000 patient years respectively ).30

Safety: weight

  • Treatment with Amaryl resulted in stable weight loss (-1.9kg.-2.9kg&-3kg at 4 months , 1 year & 1.5 years respectively) .31
  • Treatment of newly diagnosed T2DM patients with Amaryl® resulted in decrease in body weight and body mass index than treatment with Glibenclamide over 12 months.32

Mean (±SD) change in BMI (kg/m²)
Mean (±SD)change in weight (kg)
Amaryl® (n=251)
-0.71 ± 1.38
-2.04 ± -3.99
Glibenclamide (n=269)
-0.20 ± -1.28
-0.58 ± -3.65
P value for between group differences
<0.001
<0.001

Multicentre, retrospective analysis of data from case reports for 520 newly diagnosed T2DM patients treated with Amaryl® or Glibenclamide for 12 months.

 

Summary of Amaryl® safety

  • Amaryl® is safe for use in special populations than glibenclamide20,21,22
  • Amaryl® is associated with cardioprotective effects, and has low incidence of cardiovascular events compared to glibenclamide33.
  • Amaryl® maintains and Glibenclamide blunts the anti-anginal effect of ischaemic preconditioning
  • There was a low incidence of hypoglycaemia with Amaryl® than Glibenclamide in T2DM patients.
  • Amaryl® does not induce weight gain.

References:

1. Müller G, et al. Biochim Biophys Acta 1994; 1191: 267-277.
2. Del Guerra S, et al. Acta Diabetol 2000; 37: 139-141.
3 KorytkowskiM, et al. Diab Care 2002; 1607-1611
4 Schade DS, et al. J Clin Pharmacol 1998; 38: 636-641.
5 Tsunekawa T, et al. Diab Care 2003; 26: 285-289.
* Note: NOT head-to-head comparisons. Based on published data
6. Dills DG, et al. Horm Metab Res 1996; 28: 426-429.
7. Derosa G, et al. Diab Nutr Meta 2004; 17: 143-150.
8. Schernthaner G, et al. Eur J Clin Invest 2004; 34: 535-542.
9. Schade DS, et al. J Clin Pharmacol 1998; 38: 636-641.
10. Goldberg RB, et al. Diab Care 1998; 21: 1897-1903.
11. Horton ES, et al. Diab Care 2000; 23: 1660-1665.
12. Aronoff S, et al. Diab Care 2000; 23: 1605-1611.
13. Phillips LS, et al. Diab Care 2001; 24: 308-315.
14. Hoffmann J, et al. Am J Med 1997; 103: 483-490.
15. Segal P, et al. Diab Care 1997; 20: 687-691.
16. Sonnenberg GE, et al. Ann Pharmacother 1997; 31 (6): 671-676.
17. Müller G and Wied S. Diabetes 1993; 42: 1852-1867.
18. Müller G, et al. Diab Res Clin Pract 1995; 28 (suppl): S115-S137.
19. Müller G. Med Welt 2002; 53: 140-145.
20. Rosenkranz B, et al. Diabetologia 1996; 39 (12): 1617-1624.
21. Halimi s, et al. Abs:2311. 18th Int Diabetes Fed Congr (IDF) Paris (Aug 2003)
22. Shukla UA, et al. Ann Pharmacother 2004; 38 (1): 30-35.
23. Klepzig H, et al. Eur Heart J. 1999; 20: 439-446.
24. Lee TM and Chou TF. J Clin Endocrinol Metab 2003; 88: 531-537.
25. Vaur L, et al. Diabetes Metab. 2003; 29: 241-249
26. Koshiba K, et al. J Med Invest. 2006; 53 (1-2): 87-94.
27. Geisen K, et al. Horm Metab Res 1996; 28: 496-507.
28. Siluk D, et al. Diabetologia 2002; 45: 1034-1037.
29. Holstein A, et al. Diabetes Met Res Rev 2001; 17: 467-473.
30. Dills DG, et al. Horm Metab Res 1996; 28: 426-429.
31. Weitgasser R, et al. Diabetes Res Clin Pract 2003; 61: 13-19.
32. Martin S, et al. Diabetologia 2003; 46: 1611-1617.
33. Kevin.M.Pantalone Do et al,Diab Care,Vol:33;6,June 2010.

TOP

COPYRIGHT 2016 - Sanofi India Limited - ALL RIGHTS RESERVED | Sitemap | Legal Notice | Last Update: Monday, September 17, 2012