Avandia Positive ADOPT Result

GlaxoSmithKline PLC
04 December 2006

Issued - Monday 4 December 2006



     LANDMARK STUDY SHOWS AVANDIA(R) IS MORE EFFECTIVE THAN METFORMIN OR A
       SULPHONYLUREA IN LONG-TERM BLOOD SUGAR CONTROL IN TYPE 2 DIABETES



           Avandia Reduces Risk of Monotherapy Failure at Five Years



Results from ADOPT (A Diabetes Outcome Progression Trial) demonstrated that
initial treatment with Avandia(R) (rosiglitazone maleate) reduced the risk of
monotherapy failure in people with type 2 diabetes by 32 percent compared to
metformin (p<0.001), and 63 percent compared to glyburide (p<0.001) at five
years.  The results of this international study involving 4,360 people recently
diagnosed with type 2 diabetes were today published in the New England Journal
of Medicine and presented at the 19th World Diabetes Congress of the
International Diabetes Federation (IDF).1



Rosiglitazone was more effective than metformin or glyburide in delaying the
progressive loss of blood sugar control, as measured in the study by fasting
plasma glucose (FPG) and glycosylated (or glycated) haemoglobin levels (HbA1c).1
  The primary reasons for loss of blood sugar control are increasing insulin
resistance and declining beta-cell function.2  ADOPT demonstrated that
rosiglitazone significantly improved insulin sensitivity (p<0.001 versus
metformin or glyburide) and reduced the rate of loss of beta-cell function (p=0.02
versus metformin; p<0.001 versus glyburide).1



"ADOPT provides evidence supporting earlier treatment with rosiglitazone in the
management of type 2 diabetes.  This is the first long-term study to demonstrate
that the progressive loss of blood sugar control can be delayed and target blood
sugar levels can be maintained for a longer period with rosiglitazone than with
metformin and glyburide - the two most frequently prescribed oral antidiabetic
agents," said Dr Steven Kahn, professor of medicine, VA Puget Sound Health Care
System and University of Washington School of Medicine, Seattle, Washington, US
and Dr Giancarlo Viberti, professor of diabetes and metabolic medicine, King's
College London School of Medicine, UK.  "The more durable effect on blood sugar
with rosiglitazone was also consistent with greater improvements in core defects
of the disease, including significant effects on insulin resistance and beta-cell
function."



ADOPT provides an important update to findings from the United Kingdom
Prospective Diabetes Study (UKPDS) released in 1998, which preceded availability
of thiazolidinediones (TZDs) and included only two of the three oral agents
evaluated in ADOPT - metformin and sulphonylurea.3-5



Initial therapy with rosiglitazone delayed progressive loss of blood sugar
control more effectively than metformin or glyburide using different blood sugar
thresholds - from FPG >180 mg/dl (10 mmol/l) to a lower blood sugar level more
consistent with current therapeutic approaches, FPG 140 mg/dl (7.8 mmol/
l).1,6,7  Long-term blood glucose control as measured by a mean HbA1c <7.0
percent was maintained for longer with rosiglitazone - 60 months versus 45
months with metformin and 33 months with glyburide.1



"With ADOPT, we now have clear evidence from a large international study that
the initial use of rosiglitazone is more effective than standard therapies for
type 2 diabetes in maintaining blood sugar control," said Dr Lawson Macartney,
senior vice president, Cardiovascular and Metabolic Medicine Development Centre,
GlaxoSmithKline.  "ADOPT adds to the growing body of evidence released this year
supporting the rationale for incorporating rosiglitazone as a cornerstone of
treatment of type 2 diabetes by demonstrating patient benefits in terms of
long-term glucose control."



In ADOPT, rosiglitazone was reported to be generally well-tolerated among the
large cohort of people with type 2 diabetes who were followed for up to six
years.  There was no significant difference between the rosiglitazone and
metformin groups in treatment discontinuation, but the rate was higher for the
glyburide group (44 percent in the glyburide group; 38 percent in the metformin
group; 37 percent in the rosiglitazone group).  This difference was driven
largely by a higher level of withdrawals due to hypoglycaemia for people in the
glyburide group.1



The same number of congestive heart failure (CHF) serious adverse events was
reported with rosiglitazone (0.8 percent) as for metformin (0.8 percent);
however, people given glyburide experienced a lower rate of CHF events (0.2
percent).1



After the five-year period of study, commonly reported adverse events across the
treatment groups were oedema (rosiglitazone 14.1 percent; glyburide 8.5 percent;
metformin 7.2 percent); weight gain (rosiglitazone 6.9 percent; glyburide 3.3
percent; metformin 1.2 percent); gastrointestinal side effects (metformin 38.3
percent; rosiglitazone 23.0 percent; glyburide 21.9 percent); and hypoglycaemia
(glyburide 38.7 percent; metformin 11.6 percent; rosiglitazone 9.8 percent).1



Recent further analysis showed a lower rate of fractures reported as adverse
events in women taking glyburide or metformin versus rosiglitazone (glyburide
3.5 percent; metformin 5.1 percent; rosiglitazone 9.3 percent), most commonly
involving fractures of the foot and upper limb bones.1  There was no observed
difference among treatment groups in the number of fractures reported in men.1
These observed fracture rates appear to be within the range seen in a
literature-based review of observational studies in women with diabetes, and
analysis of large managed care databases.8-11  This evidence suggests that older
women with type 2 diabetes are at increased risk of fractures.8-11



S M Bicknell

Company Secretary



4th December 2006



About ADOPT

ADOPT is an international, multi-centre, randomised, double-blind study
involving 4,360 drug-naive people who had been recently diagnosed with type 2
diabetes (£ 3 years) at over 400 sites throughout North America and Europe.
People included in the study were randomised to rosiglitazone, a sulphonylurea
(glyburide), or metformin and titrated to the maximum daily effective doses
(rosiglitazone 4 mg twice daily; metformin 1 g twice daily; glyburide 7.5 mg
twice daily).  These people were followed for four to six years to examine the
long-term efficacy of each drug used as initial monotherapy on blood sugar
control, insulin resistance and b-cell function.  At the time of monotherapy
failure, 99.3 percent, 98.6 percent and 99.0 percent of participants were
receiving maximal doses of rosiglitazone, metformin and glyburide,
respectively.1



When ADOPT was designed, HbA1c was not chosen as the primary outcome because the
guidelines at the time focused largely on FPG.12  Nevertheless, HbA1c data
collected in the study as a secondary endpoint provided results, which are
consistent with those for FPG and are applicable to current clinical practice.1



ADOPT was funded by GlaxoSmithKline.



About Rosiglitazone

Rosiglitazone belongs to the thiazolidinedione (TZD) class of drugs and is an
approved treatment for type 2 diabetes that improves blood sugar control,
enabling people to reach recommended blood sugar levels.13  The addition of
rosiglitazone to metformin and/or a sulphonylurea has been shown to help people
with type 2 diabetes reach and maintain treatment goal, and findings from ADOPT
support the long-term durability of rosiglitazone monotherapy.13



About Type 2 Diabetes

Type 2 diabetes is a chronic, progressive illness often linked to premature
death, and affects approximately 230 million individuals worldwide, nearly 6
percent of the world's adult population. The IDF estimates that by 2025, more
than 350 million people worldwide will suffer from this disease.14



Type 2 diabetes occurs when the body does not respond properly to, or produce
enough, insulin.15  Over time, the chronic, progressive nature of type 2
diabetes makes it more difficult to maintain blood sugar levels and therefore,
more than one medication may be required to reach recommended goals.16,17
Keeping blood sugar levels in control is important in preventing
diabetes-related conditions such as eye disease (blindness), kidney disease
(kidney failure/dialysis), nerve damage, amputation, heart disease, stroke and
peripheral vascular disease.16,18-21  Such complications can decrease a person's
quality of life and result in increased health care costs.22  Untreated diabetes
can lead to death.  Every ten seconds, a person dies from diabetes-related
causes.23





Important Information Regarding Avandia (rosiglitazone maleate)

Globally, prescribing information varies.  Therefore, please refer to the
product label in your country for complete information.



For full European prescribing information please consult the current
rosiglitazone Summary of Product Characteristics.



About GlaxoSmithKline

GlaxoSmithKline - one of the world's leading research-based pharmaceutical and
healthcare companies - is committed to improving the quality of human life by
enabling people to do more, feel better and live longer. For company
information, visit http://www.gsk.com.



Cautionary statement regarding forward-looking statements

Under the safe harbor provisions of the US Private Securities Litigation Reform
Act of 1995, the company cautions investors that any forward-looking statements
or projections made by the company, including those made in this Announcement,
are subject to risks and uncertainties that may cause actual results to differ
materially from those projected.  Factors that may affect the Group's operations
are described under 'Risk Factors' in the Operating and Financial Review and
Prospects in the company's Annual Report on Form 20-F for 2005.



Enquiries:

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US Media enquiries:                      Nancy Pekarek           [phone]
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European Analyst/Investor enquiries:     Anita Kidgell           [phone]
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US Analyst/ Investor enquiries:          Frank Murdolo           [phone]
                                         Tom Curry               [phone]






References:

1.       Kahn SE, Haffner, SM, Heise MA, Herman WH, Holman RR, Jones NP, Kravitz
BG, Lachin JM, O'Neill C, Zinman B, Viberti G for the ADOPT Study Group.
Glycemic Durability of Rosiglitazone, Metformin, or Glyburide Monotherapy. N Eng
J Med. 2006;355:2427-2443. Published online on: December 4, 2006.

2.       Gerich JE. Redefining the clinical management of type 2 diabetes:
matching therapy to pathophysiology. Eur J Clin Invest. 2002;32:46-53.

3.       UKPDS Group. Intensive blood glucose control with sulphonylureas or
insulin compared with conventional treatment and risk of coplications in
patients with type 2 diabetes. The Lancet. 1998;352:837-853.

4.       UKPDS Group. Effect of intensive blood-glucose control with metformin
on complications in overweight patients with type 2 diabetes. The Lancet. 1998;
352:854-865.

5.       American Diabetes Association. "Rapid Increase in the Use of Oral
Antidiabetic Drugs in The United States 1990-2001." Diabetes Care, Vol. 26:
1852-1855, 2003.

6.       Harris SB, Lank CN. Recommendations from the Canadian Diabetes
Association. 2003 guidelines for prevention and management of diabetes and
related cardiovascular risk factors. Can Fam Physician. 2004; 50:425-433.

7.       Nathan DM, Buse JB, Davidson MB, et al. Management of hyperglycemia in
type 2 diabetes: a consensus algorithm for the initiation and adjustment of
therapy: a consensus statement from the American Diabetes Association and the
European Association for the Study of Diabetes. Diabetes Care. 2006; 29:
1963-1972.

8.       Schwartz AV, Sellmeyer DE, Ensrud KE, Cauley JA, Tabor HK, Schreiner
PJ, Black DM, Cummings SR. Older women with diabetes have an increased risk of
fracture: a prospective study. J Clin Endocrinol Metabol. 2001;86:32-38.

9.       de Liefde II, van der Klift M, de Laet CE, van Daele PL, Hofman A, Pols
HA. Bone mineral density and fracture risk in type 2 diabetes mellitus: the
Rotterdam Study. Osteoporos Int. 2005;16:1713-1720.

10.    Strotmeyer ES, Cauley JA, Schwartz AV, Nevitt MC, Resnick HE, Bauer DC,
Tylavsky FA, de Rekeneire N, Harris TB, Newman AB. Nontraumatic fracture risk
with diabetes mellitus and impaired fasting glucose in older white and black
adults: the health, aging, and body composition study. Arch Intern Med. 2005;
165:1612-1617.

11.    Data on file.

12.    American Diabetes Association. Standards of medical care for patients
with diabetes mellitus. Diabetes Care. 1998; 21::S23-S31.

13.    Avandia(R)  Prescribing Information.

14.    Unite for Diabetes (International Diabetes Federation). About diabetes.
Available at: http://www.unitefordiabetes.org/assets/files/About_diabetes.pdf.
Accessed on November 3, 2006.

15.    Groop LC. Insulin resistance: The fundamental trigger of type 2 diabetes.
Diabetes, Obesity & Metabolism 1999; 1 (Supplement 1):S1-S7.

16.    Stratton IM, et al. Association of glycaemia with macrovascular and
microvascular complications of type 2 diabetes (UKPDS 35): prospective
observational study. BMJ. 2000:321:405-412.

17.    Nathan DM. Initial management of glycemia in type 2 diabetes mellitus. N
Eng J Med. 2002;347:1342-1349.

18.    International Diabetes Federation. Fact Sheet: Diabetes and eye disease.
Available at: http://www.idf.org/home/index.cfm?unode=
C1CCADE9-4A03-4D17-A662-155B3ED59FDB. Accessed on November 3, 2006.

19.    International Diabetes Federation. Fact Sheet: Diabetes and kidney
disease. Available at: http://www.idf.org/home/index.cfm?unode=
BB08E3D8-4036-4C06-B654-5DC24D158820. Accessed on November 3, 2006.

20.    International Diabetes Federation. Complications of diabetes. Available
at: http://www.idf.org/home/index.cfm?node=13. Accessed on November 3, 2006.

21.    International Diabetes Federation. Fact Sheet: Diabetes and
cardiovascular disease (CVD). Available at: http://www.idf.org/home/index.cfm?
unode=FCC1DD60-2C39-4D3C-A3C0-85247F1678F3. Accessed on November 3, 2006.

22.    Unite for Diabetes (International Diabetes Federation). The economic
impact of diabetes. Available at: http://www.unitefordiabetes.org/assets/files/
Diabetes_econ_impact.pdf. Accessed on November 3, 2006.

23.    Unite for Diabetes (International Diabetes Federation). A United Nations
Resolution on diabetes. Available at: http://www.unitefordiabetes.org/assets/
files/UNR_overview.pdf. Accessed on November 3, 2006.




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