Overview of Hypertension and its

Management with Valsartan Family

(Diovan/Exforge)
Dr.Muhammad Asim Rana
HOD Medicine
Bahria International Hospital
Lahore
 Global Impact of an Elevated Hypertension 1/2

Williams B, et al. Eur Heart J. 2018;39:3021

 Hypertension* prevalence across
the globe3
France 21%
Germany 20%
Switzerland 18%
Norway
18% Russia
Canada Sweden 29%
13% UK 19%
15%

USA Spain Turkey

Italy China Japan
13% 19% 23%
20% 19% Korea 17%
Mexico Saudi Arabia India 11%
27% Thailand
21% 25%
21%
Nigeria Indonesia
Kenya
Brazil 28% 23%
28%
23%
Range <14.9% Australia
Range 15-19.9% 15%
Range 20-24.9% Argentina
Range >25% 22%

* Defined as systolic blood pressure ≥140 mmHg or diastolic blood pressure of ≥90 mmHg.
3. WHO. Global Status Report on Non-communicable diseases 2014. Available at:
http://apps.who.int/iris/bitstream/10665/148114/1/9789241564854_eng.pdf?ua=1, accessed March 27, 2017.
Pathophysiologic effects of angiotensin
II via AT1-receptor stimulation19
PAI-1/
Sympathetic thrombosis Platelet
nervous system aggregation

Superoxide
Vasoconstriction production

Aldosterone Ang II Vascular smooth

muscle growth

NaCl retention  Myocyte growth

Vasopressin Collagen
Endothelin

Ang = angiotensin; AT1 = angiotensin II type 1; NaCl = sodium choloride; PAI-1 = plasminogen activator inhibitor-1.
19. Burnier M, Brunner HR. Lancet. 2000;355:637–645.
Complex and Variable Pathophysiological
Background of Hypertension

Sympathetic nervous system

Renin-angiotensin system
Total body sodium

B. Waeber, March 2007, with permission

 Hypertension, Oxidative Stress and Angiotensin
II are the Sources of Vascular Damage

Ventricular Ventricular
remodelling dilatation
Myocardial
Heart
ischaemia
failure

Athero- End stage

sclerosis CVD

Risk
factors Death

HYPERTENSION
OXIDATIVE STRESS
ANGIOTENSIN II

CVD = cardiovascular (CV) disease

Adapted from Dzau VJ, Braunwald E. Am Heart J 1991;121:1244–63
Factors contributing to resistant
hypertension32
Lifestyle factors: Volume overload:

• Obesity • Progressive renal

• Excess alcohol intake insufficiency
• Excess dietary sodium • High salt intake
• Cocaine and amphetamine misuse • Inadequate diuretic therapy

Drug related causes: Secondary causes of

resistant hypertension:
• Non-steroidal anti-inflammatory drugs
(NSAIDs) • Primary hyperaldosteronism
• Contraceptive hormones • Renal artery stenosis
• Combined oral contraceptives are more often • Obstructive sleep apnoea
associated with elevated BP; menopausal hormone • Phaeochromocytoma
therapy has minimal effects on BP • Thyroid diseases
• Adrenal steroid hormones • Cushing’s syndrome
• Sympathomimetic agents • Coarctation of the aorta
(nasal decongestants, diet pills) • Intracranial tumours
• Erythropoeitin, cyclosporine, tacrolimus
• Liquorice (suppresses the metabolism of cortisol)
• Herbal supplements (ephedra, bitter orange, etc.)

BP = blood pressure.
32. Myat A, et al. BMJ. 2012;345:e7473.
Possible causes of secondary hypertension32,36
Cause Pertinent Features
Hypokalaemia, fatigue, low renin levels despite drug treatment that would
Primary aldosteronism be expected to elevate renin levels (i.e., ACEI, ARB, CCB, and diuretic),
usually raised aldosterone levels but elevation may not be extreme
Carotid, abdominal, or femoral bruits; history of flash pulmonary oedema;
Renal artery stenosis
young females (fibromuscular dysplasia), history of atherosclerotic disease
Obesity, short neck, daytime somnolence, snoring, frequent night time
Sleep apnea syndrome
awakenings, witnessed apnoea
Pheochromocytoma Episodic palpitations, headaches, sweating
Albuminuria or microscopic haematuria, biochemical disturbances,
Renal parenchymal disease
nocturia, oedema
Eye signs, weight loss or gain, heat or cold intolerance, heart failure,
Hypothyroidism & hyperthyroidism tachycardia, bradycardia, anxiety or fatigue. Hyperthyroidism usually
increases SBP, whereas hypothyroidism usually increases DBP
Centripetal obesity, moon facies, abdominal striae, interscapular fat
Cushing syndrome
deposition
Radio-radial or radio-femoral delay, diminished femoral pulses, rib notching
Coarctation of aorta
on chest radiograph
Oral contraceptive pills Fatigue, headaches
Liddle syndrome Fatigue, headaches, severe hypertension, young age, hypokalaemia,
Primary hyperparathyroidism Abdominal pain, bone pain, kidney stones, psychiatric issues

ACEI = angiotensin converting enzyme inhibitor; ARB = angiotensin receptor blocker; CCB = calcium channel blockers;
DBP = diastolic blood pressure; GFR = glomerular filtration rate SBP = systolic blood pressure.
32. Myat A, et al. BMJ. 2012;345:e7473; 36. Pullalarevu R, et al. Prim Care. 2014;41(4):749-64.
 Definition and Classification of Hypertension in
the Guidelines
Hypertension and stages of hypertension are not defined
JNC 81

ASH/ISH 20131

Elevated BP = SBP of 120-129 mm Hg and a DBP of less than 80 mm Hg

ACC/AHA 20172 Stage 1 hypertension: SBP of 130-139 or DBP of 80-89 mm Hg

Stage 2 hypertension: SBP ≥140 or DBP ≥90 mm Hg

High normal: SBP 130-139 mmHg and/or DBP 85-89 mmHg

Grade 1: SBP 140-159 mmHg and/or DBP 90-99 mmHg

ESC/ESH 20183
Grade 2: SBP 160-179 mmHg and/or DBP 100-109 mmHg

Grade 3: SBP ≥180 mmHg and/or DBP ≥110 mmHg

Isolated systolic hypertension: SBP ≥140 mmHg and DBP <90 mmHg
ASH = American Society of Hypertension; ESC = European Society of Cardiology; ESH = European Society of Hypertension; ISH = International Society
of Hypertension; JNC = Joint National Committee
1. James PA, et al. JAMA. 2014:311:507-520 ; 2. . Paul K. Whelton, Robert M. Carey. The 2017 Clinical Practice Guideline for High Blood
Pressure. JAMA; 3. Williams B, et al. Eur Heart J. 2018;39:3021.
 Blood pressure targets in various guidelines
BP Threshold BP Targets
BP thresholds for treatment BP goal in general BP goal in patients with BP goal in elderly
initiation population diabetes or CKD (SBP/DBP mmHg)
(SBP/DBP mmHg) (SBP/DBP mmHg) (SBP/DBP mmHg)

JNC 872 <60 yrs: 140/90 <140/90 <140/90 <150/90 (≥60 yrs)
≥60 yrs: 150/90

ACC/AHA 201750 ≥130/80 (for Clinical CVD or 10-year <130/80 <130/80 <130 SBP (≥65 yrs)
ASCVD risk ≥10%)
≥140/90 (for no clinical CVD and 10-
year ASCVD risk <10%)
≥65 yrs: ≥130 SBP
ESC/ESH 201851 ≥140/90 <140/90 (in all patients); Diabetes CKD SBP 130–139 (≥65 yrs)
130/80 (in patients who can
tolerate)
18–65 yrs: 18–65 yrs:
≤130 SBP <140-130
≥65a yrs: SBP
130-139 ≥65a yrs:
SBP 130-139
SBP
DBP: 70-79
DBP: 70-79

aTreatment decisions and blood pressure targets may need to be modified in older patients who are frail and independent.
ASCVD = atherosclerotic cardiovascular disease; ASH = American Society of Hypertension; BP = blood pressure; CSH = Chinese Society of
Hypertension; CKD = chronic kidney disease; CVD = cardiovascular disease; DBP = diastolic blood pressure; ESC = European Society of
Cardiology; ESH = European Society of Hypertension; ISH = International Society of Hypertension; JNC = Joint National Committee; SBP =
systolic blood pressure.
50. Whelton PK, et al.2017 High Blood Pressure Clinical Practice Guideline; 51. Williams B, et al. Eur Heart J. 2018;39:3021–3104;
72. James PA, et al. JAMA. 2014:311:507-520
First-step combination treatment in some
specific conditions
Preferred combination treatment Classa Levelb
Diabetes RAS blocker + CCB or diuretic I A
Coronary artery disease Beta-blocker + CCB + RAS blocker I A
Chronic kidney disease RAS blocker + CCB + diuretic (loop
diuretic)
Cerebrovascular disease RAS blocker + CCB + diuretic I A
Atrial fibrillation Beta-blocker and/or nondiCCB IIa B
Heart failure (r/p*EF) RAS blocker + beta-blocker, diuretic + IIa B
aldosterone antagonist
Chronic obstructive RAS blocker + CCB
pulmonary disease
Lower extremity arterial RAS blocker + CCB or diuretic IIa B
disease
Blacks Diuretic + CCB I B

CCB, calcium channel blocker; nondiCCB, non-dihydropiridine CCB, RAS, renin angiotensin blocker, r/p*EF, reduced/preserved ejection fraction.

Williams B, et al. Eur Heart J. 2018;39:3021–3104.

Business or Operating Unit/Franchise or Department
Overview of Valsartan
Affinity of valsartan for angiotensin receptors
compared to other angiotensin receptors
blockers*

Drug AT1 versus AT2 affinity

Valsartan104 ~20,000-fold

Telmisartan106 >3000-fold

Irbesartan107 >8500-fold

Azilsartan108 >10,000-fold

Olmesartan109 >12,500-fold

Losartan110 ~1000-fold

* Affinity of each angiotensin receptor blocker was assessed in separate experiments.

AT1 = angiotensin II type 1 (AT1) receptor antagonist; AT2 = angiotensin II type 2 (AT2) receptor antagonist.
105. Valsartan Prescribing Information. Novartis Pharmaceuticals Corp. July 2015; 106. Telmisartan Prescribing Information.
Boehringer Ingelheim Pharmaceuticals, Inc. Dec 2014; 107. Irbesartan Prescribing Information. Sanofi-Aventis LLC. May 2014; 108.
Azilsartan Prescribing Informatio. Arbor Pharmaceuticals. Oct 2016; 109. Olmesartan Prescribing Information. Daiichi Sankyo, Inc.
Sept 2014; 110. Losartan Prescribing Information. Merck & Co. Inc. Dec 2015.
 VALUE (Valsartan Antihypertensive Long-term Use
Evaluation) study overview 114,117

To determine if, for the same BP control, valsartan reduces CV

Objective
morbidity and mortality more than amlodipine

• BP-reducing effects more pronounced with Aml over Val

• Rates of MI, heart failure and stroke were similar between the two
groups. Rates of new onset diabetes were higher in the Aml-
Results
group.

• Both treatment strategies were well tolerated with few severe AEs.
Edema/peripheral edema was twice as common in the Aml-group.

* One month and out to one year.

AEs = adverse events; Aml = amlodipine; ACEI = angiotensin-converting enzyme inhibitor; ARB = angiotensin II receptor blocker; BP = blood
pressure; CCB = calcium channel blocker; CI = confidence interval; CV = cardiovascular; HCTZ = hydrochlorothiazide; HR = hazard ratio; HTN
= hypertension; MI = myocardial infarction; od = once daily; Val = valsartan.
114. Julius S, VALUE trial group. Lancet. 2004;363(9426):2022-31; 117. Schmieder RE, et al. J Hypertens. 2008;26(3):403-11.
 VALIANT (Valsartan In Acute myocardial iNfarction Trial)
study overview 119

To compare the effects on mortality of valsartan, captopril, and a

Objective combination of the two in patients with MI complicated by left
ventricular systolic dysfunction, heart failure, or both

Valsartan is as effective as captopril in reducing

Results
all-cause mortality in patients post-myocardial infarction

* The difference from the captopril group was significant at p<0.05.

AE = adverse event; bid = twice daily; Cap = captopril; CI = confidence interval; MI = myocardial infarction; tid = three-times daily;
Val = valsartan. 119. Pfeffer MA, VALIANT Investigators. N Engl J Med. 2003;349:1893–906.
 Val-HeFT (Valsartan Heart Failure Trial)
study overview 121

To evaluate the long-term effects of the addition of Val to standard

Objective
therapy for heart failure

• Val group had significant improvements in NYHA class, ejection

fraction, signs and symptoms of heart failure.
Results

ACEI = angiotensin-converting enzyme inhibitor; bid = twice daily; CI = confidence interval; HF = heart failure;
NYHA = New York Heart Association; QoL = quality of life; RR = relative risk; Val = valsartan.
121. Cohn JN, Valsartan Heart Failure Trial Investigators. N Engl J Med. 2001;345:1667–75.
 MARVAL (MicroAlbuminuria Reduction with VALsartan)
study overview128

To evaluate the BP-independent effect of Val on UAER in type 2

Objective
diabetic patients with microalbuminuria

• Both valsartan and amlodipine reduced blood pressure to a

similar extent.

• Valsartan was significantly more effective than amlodipine in

Results
reducing urine albumin excretion.

• Significantly higher proportion of valsartan-treated patients

returned to normoalbuminuria* by week 24.

Aml = amlodipine; BP = blood pressure; CI = confidence interval; HTN = hypertension; od = once daily;
RAAS = renin-angiotensin-aldosterone system; UAER = elevated urine albumin excretion; Val = valsartan.
128. Viberti G, MARVAL Study Investigators. Circulation. 2002;106(6):672-8.
Fixed Dose Combination
 Greater number of antihypertensive agents are
needed to reach blood pressure goal55-59

AASK = African American Study of Kidney Disease and Hypertension; ABCD = Appropriate Blood Pressure Control in Diabetes; ACCOMPLISH
= Avoiding Cardiovascular Events through Combination Therapy in Patients Living with Systolic Hypertension; ALLHAT = Antihypertensive and
Lipid-Lowering Treatment to Prevent Heart Attack Trial; ASCOT-BPLA = Anglo-Scandinavian Cardiac Outcomes Trial-Blood Pressure Lowering
Arm; BP = blood pressure;
HOT = Hypertension Optimal Treatment; IDNT = Irbesartan Type II Diabetic Nephropathy Trial; MDRD = Modification of Diet in Renal Disease;
RENAAL = Reduction of Endpoints in Non-insulin-dependent diabetes mellitus with the Angiotensin II Antagonist Losartan; UKPDS = UK
Prospective Diabetes Study. 55. Bakris GL. Am J Med. 2004;116(Suppl 5A):30S–38S; 56. Dahlöf B, ASCOT Investigators. Lancet.
2005;366:895–906;
57. Jamerson K, ACCOMPLISH Investigators. Blood Press. 2007;16:80–6; 58. Jamerson K, ACCOMPLISH Trial Investigators. N Engl J Med.
2008;359:2417–2428.
Fixed-dose combinations offer several advantages vs
free combinations59,60

BP = blood pressure; FDC = fixed-dose combination.

59. British Hypertension Society. September 2012; 60. Mallat SG, et al. Integr Blood Press Control. 2013;6:69–78.
 Multiple-mechanism therapy results in greater
blood pressure reduction than seen with single-
mechanism components61-63

ARB = angiotensin receptor blocker; BP = blood presssure; CCB = calcium channel blocker; CHF = congestive heart failure;
RAAS = renin–angiotensin–aldosterone system. 61. Sica DA. Drugs. 2002;62:443–462; 62. Quan A, et al. Am J Cardiovasc Drugs. 2006;6:103–113;
63. Destro M, et al. Vasc Health Risk Manag. 2010;6:253-60.
Amlodipine/valsartan real world
data
EXCITE (clinical EXperienCe of amlodIpine and valsartan in
hypErtension) study overview201
To evaluate the effectiveness, tolerability and adherence of Aml/Val and
Objective Aml/Val/HCTZ therapies in patients with HTN from the Middle East and
Asia studied in routine clinical practice
• Significant blood pressure reductions were observed across all
hypertension severities with amlodipine/valsartan therapy.

• Significant blood pressure reductions with amlodipine/valsartan were

observed across prior antihypertensive monotherapy classes.

Results • Amlodipine/valsartan showed significant blood pressure reductions in

diverse patient subgroups

* Middle East: Bahrain, Egypt, Kuwait, Lebanon, Oman, Qatar, and United Arab Emirates; Asia: Indonesia, Hong Kong, Pakistan,
Philippines, South Korea, and Taiwan;
† SBP <140 mmHg and DBP <90 mmHg or SBP <130 mmHg and DBP <80 mmHg in patients with co-morbid diabetes. ACEI =

angiotensin converting enzyme inhibitor; AEs = adverse events; Aml = amlodipine; ARB = angiotensin II receptor blockers; BP = blood
pressure; CCB = calcium channel blocker; CI = confidence interval;
DBP = diastolic BP; HCTZ = hydrochlorothiazide; HTN = hypertension; ISH = isolated hypertension; MSDBP = mean sitting diastolic BP;
MSSBP = mean sitting systolic BP; SBP = systolic BP; Val = valsartan. 201. Sison J, et al. Curr Med Res Opin. 2014;30:1937–45.
 Significant blood pressure reductions were observed across
all hypertension severities with amlodipine/valsartan
therapy201

BP = blood pressure; EXCITE = clinical EXperienCe of amlodIpine and valsarTan in hypErtension;

MSDBP = mean sitting systolic BP; MSSBP = mean sitting systolic BP; SBP = systolic BP.
201. Sison J, et al. Curr Med Res Opin. 2014;30:1937–45.
 Significant blood pressure reductions with amlodipine/valsartan
were observed across prior antihypertensive monotherapy
classes202

ACEI = angiotensin-converting enzyme inhibitor; ARB = angiotensin receptor blocker; BP = blood pressure;
CCB = calcium channel blocker; EXCITE = clinical EXperienCe of amlodIpine and valsarTan in hypErtension;
MSDBP = mean sitting systolic BP; MSSBP = mean sitting systolic BP.
202. Assaad-Khalil SH, et al. Vasc Health Risk Manag. 2015;11:71-8.
 Amlodipine/valsartan showed significant blood
pressure reductions in diverse patient subgroups202

BP = blood pressure; EXCITE = clinical EXperienCe of amlodIpine and valsarTan in hypErtension;

ISH = isolated hypertension; MSDBP = mean sitting systolic BP; MSSBP = mean sitting BP.
202. Assaad-Khalil SH, et al. Vasc Health Risk Manag. 2015;11:71-8.
 Blood pressure goals and response achieved in diabetic
and non-diabetic patients201

* SBP <130 mmHg, DBP <80 mmHg † SBP <140 mmHg, DBP <90 mmHg
Aml = amlodipine; BP = blood pressure; DBP = diastolic BP; EXCITE = clinical EXperienCe of amlodIpine and valsarTan in
hypErtension; HCTZ = hydrochlorothiazide; SBP = systolic BP; Val = valsartan.
201. Sison J, et al. Curr Med Res Opin. 2014;30:1937–45.
 Meaningful blood pressure reductions from baseline were
observed across hypertension severities
with amlodipine/valsartan/HCTZ triple therapy201

Aml = amlodipine; BP = blood pressure; EXCITE = clinical EXperienCe of amlodIpine and valsarTan in hypErtension;
HCTZ = hydrochlorothiazide; MSDBP = mean sitting diastolic BP; MSSBP = mean sitting systolic BP; SBP = systolic BP; Val = valsartan.
201. Sison J, et al. Curr Med Res Opin. 2014;30:1937–45.
 Amlodipine/valsartan/HCTZ triple therapy showed
significant blood pressure reductions in diverse patient
subgroups202

BP = blood pressure; EXCITE = clinical EXperienCe of amlodIpine and valsarTan in hypErtension; HCTZ = hydrochlorothiazide;
ISH = isolated hypertension; MSDBP = mean sitting diastolic BP; MSSBP = mean sitting systolic BP.
202. Assaad-Khalil et al. Vasc Health Risk Manag. 2015;11:71-8.
 Amlodipine/valsartan/HCTZ was well-tolerated
in observational study201
Aml/Val Aml/Val/HCTZ Total
n=8,603 n=1,191 N=9,794
AEs by preferred term* n (%) n (%) n (%)

SAEs 49 (0.6) 1 (0.1) 50 (0.5)

Total AEs 963 (11.2) 73 (6.1) 1036 (10.6)

Edema 173 (2.0) 39 (3.3) 212 (2.2)

Peripheral edema 99 (1.2) 9 (0.8) 108 (1.1)

Headache 87 (1.0) 2 (0.2) 89 (0.9)

Cough 52 (0.6) 3 (0.3) 55 (0.6)

Nausea 41 (0.5) 2 (0.2) 43 (0.4)

• Most of the AEs and SAEs were assessed by the study investigators as being unrelated to the
medication of interest

• Thirteen deaths were reported during the study, none of which were considered by investigators to be
related to the medication of interest

* Events occurring in ≥0.5% of any treatment group safety set.

AEs = adverse events; Aml = amlodipine; BP = blood pressure; EXCITE = clinical EXperienCe of amlodIpine and valsarTan
in hypErtension; HCTZ = hydrochlorothiazide; SAEs = serious adverse event; Val = valsartan.
201. Sison J, et al. Curr Med Res Opin. 2014;30:1937–45.
Vildagliptin Efficacy in Combination
with Metformin for Early Treatment
(ETI) of Type II Diabetes

34 Business Use Only

 A new treatment approach to early
1,2

T2DM?
Current stepwiseapproach New approach: early OAD combination

10 10

9 9
HbA1c level

HbA1c level
8 8

7 7

6 6

T2DM duration T2DM duration

OAD, oral antidiabetic agent; left diagram adapted from reference 2; right diagram is a theoretical representation of the potential impact of adding in earlier OAD combination to HbA1c levels (not representative of VERIFY study findings)
*injectable therapy

➔
 A 5 year study in early T2DM
comparing two treatment strategies 1,9

Baseline HbA1c: Newly-diagnosed 5-year study

6.5 – 7.5% Metformin run-in

Period 1 Period 2 Period 3

Early combination strategy
MET 500 mg/d

MET 1000 mg/d

MET 1500 mg/d

Vilda 50 mg bid + Vilda 50 mg bid + + (basal)insulin*

RANDOMIZATION

MET up to 1000 mgbid MET up to 1000 mg bid

HbA1c ≥7.0% (twice) At investigator discretion

Screening Run-in 3weeks Placebo bid + Vilda 50 mg bid +

2 weeks
MET up to 1000 mg bid MET up to 1000 mg bid
+ (basal) insulin*
n~2001 Sequential metformin monotherapy strategy

Day 1 Visits every 3 months 5-Year Study

Primary endpoint: time to confirmed initial treatment failure (HbA1c ≥7%)

MET, metformin; Vilda, vildagliptin; bid, twice daily; *insulin initiation according to local guidelines

➔
VERIFY represents .... the real life patients5
34
countriesover

5
continents

Europe

52% Asia

17%
Latin
America
Africa
27% 3% Australia

1%

➔
12
Your early T2DM patients can enjoy better glycemic control
with an early combination strategy9

• VERIFY’ed: 1 in 2 early T2DM patients are well controlled for at least 5 years

56%
38% HbA1c <7%
at 5 years
p<0.001 vs. met
mono

Patients onmet
mono strategy* Data
Patients on early
*Treatment success = HbA1c <7%; % patients shown derived from proportion of patients with HbA1c ≥7%
vilda/met strategy*

➔
➔
19
Early combination strategy brings
improved glycemic control 9
Primaryendpoint: Time to confirmed initialtreatment failure(HbA1c ≥7%)
Treatmentsstartedat randomization
75% met mono
Proportion of patients with HbA1c >7%

vilda/met

50%

25%

Hazard ratio (95% CI): 0.51 (0.45, 0.58), p<0.0001

0%

0 0.5 1 1.5 2 2.5 3 3.5 4 4.5 5

Time (years)
Period 2data
Graph adapted from reference 9; Analysis using full analysis dataset. Cox regression analysis – hazard ratio (95% CI): 0.51 (0.45, 0.58)

➔
Your patients can be more successful with early
combination, compared to adding vildagliptinlater9

Time to second treatment failure(HbA1c ≥7%) in subsequent period

Patientson differenttreatmentstrategies nowallreceivingvilda/met(Period2)
50%

met mono
Proportion of patients with HbA1c >7%

vilda/met

25%

Hazard ratio (95% CI): 0.74 (0.63, 0.86), p<0.0001

0%

0 0.5 1 1.5 2 2.5 3 3.5 4 4.5 5

Time (years)

Graph adapted from reference 9; Analysis using full analysis dataset. Cox regression analysis

➔
21
Your patients have 2 extra years of glycemic control*
with the early combination strategy9

• VERIFY’ed: Durable treatment success (HbA1c <7%) withcombination

Mediandurationof glycemic control(HbA1c <7%), by treatmentarm*

Met mono strategy, ~3years

Early vilda/met strategy, 5+years

vilda/met: n=983; met mono: n=989

Additional 2+ years

Data
*Derived from time over which 50% of patients in each group were at HbA1c ≥7% based on best estimates from the graphical representation in reference 9

➔
➔
22
3 out of 4 patients on vilda/met achieve HbA1c <6.5%
at 3 months and keep it for at least a year 10
% of patientsat HbA1c <6.5%
75%
75%
vilda/met
Proportion of patients with HbA1c <6.5%

met mono

54%

50%

25%

0 0.5 1 1.5 2 2.5 3 3.5 4 4.5 5

Time (years)

*Percentages given are best estimates from the graphical representation of the data in reference 10; graph adapted from reference 10

➔
Strict glycemic control in the first year
improves future T2DM outcomes8
Risk reductionfrom HbA1c levels <6.5% vs. between7- 8% in firstyear, in a studywith13-year follow-up8

Microvascular Macrovascular Death

↓39% ↓29% ↓29%

p<0.0001 p<0.0001 p<0.001

HbA1c <6.5% (n=864); <7-8% (n=385); microvascular: end-stage renal disease, advanced eye disease, amputation; macrovascular: stroke, heart disease/failure, vascular disease

➔
Early combination strategy enables more patients to
continuously achieve pre-diagnostic HbA1c levels over
5 years10
% of patientsat HbA1c <6.5%
75%
vilda/met
Proportion of patients with HbA1c <6.5%

met mono

50%

40%

28%

25% 5 years
0 0.5 1 1.5 2 2.5 3 3.5 4 4.5 5

Time (years)

*Percentages given are best estimates from the graphical representation of the data in reference 9; graph adapted from reference 10

➔
Favorable glycemia outcomes in often
difficult-to-treat ethnic groups9,11

% reduced relative risk of glycemic failure(HbA1c ≥7%) over the studyfromuse of

earlycombinationstrategyversus monotherapystrategy*
Native
Overall Caucasian Black Asian American Other
(n=1043) (n=647) (n=25) (n=173) (n=113) (n=85)

37%
46%
49% 55%
60%

77%
vilda/met

Percentages derived from hazard ratio of proportion of patients failing (HbA1c ≥7%) over 5 years; n, total number of patients in each racial group
*Predefined subgroup analysis of the primary endpoint expressed as relative risk reduction based on hazard ratios.

➔
33
A well tolerated early T2DM combination
treatment for longer control 9

• VERIFY’ed: Early vilda/met strategy was well tolerated, and well adhered to,
over the 5 years

Adverse event No weight gain

High number No increased risk
Discontinuation (AE) profiles over 5 years
of patients of hypos despite
rates low and similar for both (average 1 kg
completed the low glycemia
comparable treatment reduction
study levels
strategies in both groups)

Data Data Data Data Data

➔
➔
Galvus Met® (vildagliptin/metformin) offers a
new treatment approach for early T2DM

#OurFutureVERIFYed
➔
Refere
nces
1.Del Prato S, et al. Diab Med. 2014;31:1178-84
2.Khunti K, et al. Diabetes Care. 2013;36:3411-17
3.DeFronzo RA. Am J Med. 2010;123(3 Suppl):S38-48
4. UKPDS 34. Lancet. 1998;352:854-65

5. Matthews DR, et al. Diabet Med. 2019;36:505-13 (and supplementary appendix)

6. Hackett E & Jacques N. Clinical Pharmacist. 2009;1:4
7. Holden SE, et al. Diab Med. 2017;34(6):770-80
8. Laiteerapong N, et al. Diabetes Care. 2019;42:416-26
9. Matthews DR et al. (e-pub ahead of print Sep 18, 2019) The Lancet
10. Matthews DR et al. (e-pub ahead of print Sep 18, 2019) The Lancet (supplementary appendix)
11. Spanakis EK and Hill Golden S. Curr Diab Rep. 2013;13(6):1-18

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43