"It is now time for a paradigm shift in the treatment of Type 2 diabetes by assessing the individual patient’s risk by determining the inflammatory status and develop drugs that not only sustain the beta cell function but can also be evaluated as a prophylactic therapy."

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“Get Real and Get It Right” with Type 2 diabetes: It Is Time For
A Paradigm Shift
TriGlytzaÔ: A Potential Gamechanger for Type 2 diabetes Patients
Ravi Kumar, Ph.D. Founder and CEO, ARKAY Therapeutics
Mission Statement: Develop Clinically Superior Yet Affordable Innovative Products
That Provide Sustained Glycemic Control For Type 2 diabetes Patients Worldwide.
Executive Summary
ARKAY Therapeutics is a privately-held clinical stage biopharmaceutical company located
in East Windsor, NJ. Type 2 diabetes, a leading cause of death worldwide is an
independent risk factor for a variety of diseases including: cardiovascular disease, several
types of cancers and neurological disorders. Type 2 diabetes continues to be an unmet
medical need because the currently marketed treatment options do not adequately treat
the underlying multidimensional pathophysiology. In real-world clinical practice in the
United States, the first-line of therapy, second and third add-on drugs failed in almost 50%
of the newly diagnosed patients between 2006 and 2016. These drugs were approved for
treating primarily the symptoms as indicated by reductions in the HbA1c levels and not for
mitigating the underlying pathophysiology of progressive deterioration of pancreatic beta
cell function. They are inadequate in filling one of the most important clinical gaps in the
Type 2 diabetes space: sustained glycemic control with a focus on preventing pancreatic
beta cell failure and decreasing insulin resistance. To fill this important gap, ARKAY
Therapeutics is developing an innovative, rationalized and patient-centric product called
RK-01 or TriGlytzaÔ. It is custom-designed and formulated to target multiple distinct and
overlapping pro-inflammatory signaling pathways along the RAS-IL1b-Cox2-PGE2-EP3
axis that contribute to progressive deterioration of beta cell function and insulin resistance,
the core defects in all patients. The scientific rationale and the product concept are
supported by the results obtained from translational animal models as well as controlled
clinical studies. They have been endorsed by leading experts in the diabetes and
cardiovascular disease space. ARKAY is currently raising capital for an FDA-approved
clinical study (ClincialTrials.gov ID: NCT03686657) to evaluate the superiority of RK-01
prototype over Metformin, the current standard of care in newly diagnosed drug naïve and
obese Type 2 diabetes patients with inadequate glycemic control with Metformin
monotherapy. TriGlytzaÔ represents a paradigm shift in the clinical management of Type
2 diabetes and it is a potentially disruptive product.
Scientific Rationale and The Product Concept
The march of diabetes has been relentless. Diabetes patient population has almost
doubled between 1980 and 2014 worldwide (Statista). It is not showing any signs of
slowing down. Over 90% of diabetes patients have Type 2 diabetes which is characterized
by insulin resistance and pancreatic beta cell dysfunction. There are over 26 million Type
2 diabetes patients in the United States alone and it is expected to grow to over 40 million
by 2040 (IDF, Facts and Figures). Over 1.3 million people are diagnosed with Type 2
diabetes every year in the United States alone. The prevalence of prediabetes is three
times that of Type 2 diabetes. A Third of the U.S. population or over 86 million people
have prediabetes. The Type 2 diabetes population is expected to double to over 600

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million worldwide by 2045 (Figure 1). The current global economic burden is over $2.3T.
Diabetes along with the cardiovascular diseases is the third leading cause of death in the
United States (ADA, CDC, Biovision). The global Type 2 diabetes market is expected to
grow from $20.4B to over $58.7B in 2025 (FiercePharma). The burden of Type 2 diabetes
or the risk of incidence for cancers such as breast, rectum, pancreas, liver and gall bladder
is over 35% because it is an independent risk factor (Zhao, X-B. et al. 2016; Ballatori, P.
et al. 2017). Recent publications have highlighted the risk of developing diseases such as
Alzheimer’s disease, Parkinson’s disease and depression in diabetes patients. The link
between insulin resistance of the brain cells and Alzheimer’s disease is so strong that
some have proposed classifying it as Type 3 diabetes (Kandimalla, R. et al. 2017).
The current treatment guidelines and algorithms of AACE, ADA and EASD provide an
extremely valuable tool and a roadmap for treating diabetes patients but unfortunately,
they are designed to fail in real-world clinical practice due to the complex dynamic among
patients, healthcare providers (HCPs) and the Health Care System (HCS) barriers.
Multiple factors contribute to the clinical inertia that occurs after the failure of Metformin,
the current first line of therapy as a result of the delay in the treatment intensification which
prevents patients from reaching their target goals for HbA1c levels (Okemah, O. et al.
2018). HbA1c is the surrogate marker and a measure of blood glucose levels. Failure to
meet patient-specific HbA1c goals put patients on a certain path to diabetes-related
microvascular complications such as retinopathy, neuropathy and nephropathy,
macrovascular complications such as stroke, peripheral artery disease (PAD), Coronary
Artery Disease (CAD). Inadequate glycemic control is responsible for over 200,000 cases
of diabetes-related complications per year in North America alone (Strain, W.D. et al.
2014). The currently marketed treatment options have focused on changing the hepatic
glucose output, insulin sensitization, direct stimulation of beta cells, or reducing the
glucose reabsorption in the kidneys. In real world clinical practice, a study that examined
trends and intensification in the use of antidiabetes drugs in over 1,023,340 adults
between 2006 and 2016 in the United States reported that the proportion of patients using
Metformin as the first-line of therapy increased from 60% in 2005 to 77% in 2016 and
antidiabetes drugs failed in almost 50% of the newly diagnosed patients (Montvida, O. et
al. 2018). In patients prescribed Metformin as the first-line of therapy, 48% initiated a
second add-on treatment at a mean HbA1c of 8.4%. Among the 78% of patients who had
at least 1-year follow-up after starting a second antidiabetes medication, 52% were
prescribed a third agent. The discontinuation rates in the first year were highest among
SGLT2 inhibitors (25%), followed by TZDs (21%), GLP-1 receptor agonists (21%) and
DPP-IV inhibitors (18%). Failure occurs because they were designed to treat and
approved based primarily on their ability to treat the symptoms such as HbA1c and not for
mitigating the underlying pathophysiology of progressive deterioration of pancreatic beta
cell function, the core defect in all patients. Beta cells in the Pancreas have an inherent
capacity for compensating for elevated blood glucose levels or hyperglycemia and insulin
resistance by secreting required amount of insulin. In spite of therapy with the current
treatment options, beta cell mass progressively decreases and their function continues to
deteriorate compromising their ability to compensate for hyperglycemia and insulin
resistance. Patients gradually reach a state of insulin dependence, a stage at which insulin
therapy becomes the only treatment option and at this stage Type 2 diabetes becomes
indistinguishable from Type 1 diabetes. It is important to note that the progressive nature

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of Type 2 diabetes is not due to an increase in insulin resistance but rather due to
progressive decline in beta cell function. Based on the results from numerous clinical
studies (Vanik, A.I. 2004), it is now time for a paradigm shift in the treatment of Type 2
diabetes by assessing the individual patient’s risk by determining the inflammatory status
and develop drugs that not only sustain the beta cell function but can also be evaluated
as a prophylactic therapy.
Source: IDF.ORG
Figure 1: Global diabetes emergency due to the unrelenting march of diabetes. Number
of people with diabetes worldwide and per region, 2017 vs. 2045 (Ages 20-79 years).
Source: IDF
Type 2 diabetes is a progressive inflammatory disease and inflammation is central to the
pathophysiology (Vinik, A.I. 2004; Skyler, J.S. et al. 2017). It has a multifactorial and
multidimensional pathophysiology but the unifying pro-inflammatory signaling pathways
that originate from a variety of clinically relevant tissues along the RAS-IL1b-Cox2-PGE2-
EP3 axis (Figure 2) contribute to progressive deterioration of pancreatic beta cell function,
the core defect or the “final common denominator” (Schwartz, S. et al. 2016). Pro-
inflammatory signals originating from multiple clinically relevant cell types and tissues due
to the multifactorial pathophysiology trigger apoptosis or programmed cell death of beta
cells and degrade their capacity to respond adequately to the elevated blood glucose
levels (Figure 3 and 4). Pro-inflammatory signals contribute to the pathophysiology of
diabetes complications as well (Skyler, J.S. et al. 2017). From a clinical perspective, it is
important to note that over 85% of Type 2 diabetes patients have high blood pressure
(ADA, Facts and Figures) and over 47% of the adults with Type 2 diabetes also have
arthritis as a coexisting condition (arthritis.org). Activation of Renin-Angiotensin System

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or RAS and Cyclooxygenase-2 or Cox-2-mediated cascade of signaling pathways
contribute to high blood pressure and arthritis or degenerative joint disease, respectively.
Activation of RAS in the context of pancreatic beta cells has nothing to do with high blood
pressure but it is in fact pro-inflammatory. It contributes along with Cox-2 mediated
elevation in PGE2 to reduction in the beta cell mass and progressive deterioration of beta
cell function. The dose-dependent elevation in PGE2 levels and reduction in the beta cells
ratio/islet (Oshima, H. et al. 2006) in a transgenic mouse model (Figure 5) is supported by
an increased production of PGE2 isolated from islets obtained from donors with Type 2
diabetes patients compared to non-diabetic donors (Kimple, M.E. et al. 2013).
Figure 2: Pro-inflammatory pathophysiology of Type 2 diabetes: RAS-IL1b-Cox2-PGE2-
EP3 axis
Furthermore, a cross-sectional view of an initial cohort study data revealed that PGE2
levels, a potent inhibitor of insulin secretion, predicted lack of effectiveness of GLP-1
analogs and DPP-IV inhibitors in Type 2 diabetes patients (Fenske, R. et al. 2017). The
clinical significance of PGE2 is further supported by suppression of GLP-1 mediated
insulin secretion by PGE2 analog Sulprostone (EP3 agonist) and it was overcome by an
EP3-specific antagonist, L-798106 (Kimple, M.E. et al. 2013). Therefore, for efficient
clinical management, an innovative and rationalized drug combination such as TriGlytzaÔ
that can provide sustained glycemic control with a focus on preventing beta cell failure,
decreasing insulin resistance, preventing or delaying insulin therapy and delaying or
preventing diabetes complications in the context of comorbidities such as high blood

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pressure and a coexisting condition such as arthritis is essential and it makes perfect
clinical sense.
Source: Skyler, J.S. et al. 2017
Figure 3: Multidimensional and multifactorial pathophysiology of Diabetes

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Metformin is the “Gold Standard” and the current standard of care for Type 2 diabetes
patients. It also is the current first line of therapy. Metformin’s efficacy is insulin dependent
and it becomes ineffective as beta cell function deteriorates to a state of insulin
Source: Schwartz, S. et al. 2016
Figure 4: b-cell-centric construct: Targeted therapies for preserving beta cells and
decreasing insulin resistance.
insufficiency in spite of therapy. It is an off-patent drug and it is highly affordable world-
wide. All the drugs that have been approved for Type 2 diabetes were approved as an
add-on drug to Metformin because they were evaluated in patients on Metformin
background. Therefore, it makes not only the clinical sense but more importantly, an
economic sense to develop a product that sustains the efficacy of Metformin and is also
affordable worldwide. In real-world clinical practice, it is not just the clinical superiority that
matters but what patients can afford and what they are willing to take matters more. There
is no doubt that some great new drugs have reached the market in recent years such as
GLP-1s e.g. Novo Nordisk’s Victoza, SGLT2 inhibitors e.g. Eli Lilly/Boehringer Ingelheim’s
Jardiance and DPP4 inhibitors e.g. Merck’s Januvia. Some of these drugs have
differentiated themselves by not only lowering blood glucose levels but more importantly
by reducing the risk of cardiovascular disease. But unfortunately, these drugs and the
mechanisms they target do not have an inherent anti-inflammatory capacity to maintain
or restore beta cell function long term. They do appear to improve the beta cell function
short term indirectly due to reduction in the stress on the beta cells as a consequence of
lowering of the blood glucose levels. It is not sustainable as indicated by the failure of the

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second and third add-on drugs in real-world clinical practice in almost 50% of the patients
in the United States (Montvida, O. et al. 2018).
Source: Oshima, H. et al. 2006
Figure 5: Fluorescence immunostaining of the islets for insulin (b-cell; Green) and
glucagon (a-cell;red). Shown are results of two islets from each for the wild-type (A), RIP-

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C2 (Cox2)mE(mPGES) (Tg/–) mice (B), RIP-C2mE (Tg/Tg) mice (C). Scale bars, 100 µm.
Shown in the bottom panel ratio of b-cells (D) and a-cells (E) to the total islet cells (mean
±S.E.) *, p<0.05.
To fill this clinically important gap, ARKAY Therapeutics is developing a uniquely
formulated proprietary product, RK-01 or TriGlytzaÔ by using a dual combination of
Celecoxib, a Cox-2 inhibitor and Valsartan, an Angiotensin II Type 1 receptor blocker
which is also a RAS blocker as an add-on or as an adjunctive therapy to Metformin.
Celecoxib or CelebrexÒ is currently approved for treating Arthritis and Valsartan or
DiovanÒ is currently approved as an anti-hypertensive drug. They both are being
repurposed for treating Type 2 diabetes. Results from the controlled clinical studies with
Type 2 diabetes patients (El-Bahrawy, H. et al. 2017; Gonazalez-Ortiz, M. et al. 2005;
Goossens, G.H. et al. 2012; Mendez del Villar, et al. 2017; Pscherer, S. et al. 2010;
Ramos-Zavala, M. et al. 2011; van der Zijl, N.R. et al. 2011) as well as from appropriate
animal models (Fujita, H. et al. 2007; Cole, B.K. et. Al. 2010; Kumar, R. ADA Conference
2016 and Diabetes 2016; Lu, C.H. et al. 2016) have shown that they improve beta cell
function, first and second phase of insulin secretion, lower HbA1c levels, improve insulin
sensitivity, inflammatory, lipid and atherogenic parameters. ARKAY has adopted a
505(b)(2) regulatory strategy for the clinical development of the commercial proprietary
formulation of TriGlytzaÔ. This strategy reduces the cost and the time of development
and enables competitive pricing worldwide. The cost of development is expected to be
only a fraction i.e. about 20% or $200M vs. >$1B compared to the development of a new
molecular entity or NCE. ARKAY has mitigated the risk to a great extent because there is
already human proof-of-concept (PoC) from controlled clinical studies and the component
drugs have a track record of safety for chronic use in the Type 2 diabetes space. Unlike
the currently marketed treatment options which treat Type 2 diabetes in isolation,
TriGlytzaÔ is custom-designed to treat the disease in the context of comorbidities and
coexisting conditions. The clinical study protocol is designed with unique sets of patient
populations, primary and secondary outcome measures that would help TriGlytzaÔ to
differentiate from currently marketed drugs and facilitate unique labeling upon approval
by the FDA (Kumar, R. 2018, ClinicalTrials.gov ID: NCT03686657).
The U.S. FDA has approved or cleared the ARKAY’s IND (Investigational New Drug)
application for evaluating the superiority of TriGlytzaÔ over Metformin in drug naïve newly
diagnosed and obese Type 2 diabetes patients with inadequate glycemic control with
Metformin monotherapy, ClinicalTrials.gov ID: NCT03686657. The U.S. patent office
(USPTO) has issued ARKAY a patent, US 9,839,644 which protects the formulations and
the method used for TriGlytzaÔ. ARKAY has also filed a continuation patent application
which protects additional adjunctive or add-on formulations of RK-01 to drugs such as
GLP-1s, SGLT2 inhibitors and DPP-IV inhibitors. The pipeline of ARKAY also includes
repurposing of RK-01 for orphan diseases such as NASH (Non-alcoholic Steatohepatitis)
and PCOS (Polycystic Ovarian Syndrome). ARKAY Therapeutics was recently
announced as a finalist for the CARE (Clinical and Research Excellence) award. The
winners will be announced at an award ceremony event on May 2nd
in Boston, MA. Based
on the results obtained from controlled clinical studies with the component drugs, we
expect TriGlytzaÔ to prevent Metformin failure by maintaining a state of insulin sufficiency

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and mitigate the clinical inertia. Our long term goal is to replace Metformin with TriGlytzaÔ
as the first line of therapy. It will also be evaluated for reducing the risk of developing Type
2 diabetes in prediabetes patients in a future clinical trial.
The scientific rationale and the product concept have been endorsed by leading
endocrinologists and experts in the metabolic and cardiovascular disease space; some of
them have joined ARKAY’s management team, the board and the scientific advisory
committee. One of them is Stan Schwartz, MD, a renowned endocrinologist, and expert
in cardiometabolic syndrome and an Emeritus Associate Clinical Professor, University of
Pennsylvania. Dr. Schwartz developed the pancreatic ‘beta-cell-concept’ for reclassifying
diabetes as well as for efficient clinical management of diabetes by stratifying patients
based on the defects and mechanisms that contribute to beta cell dysfunction. Beta cell
dysfunction is the core defect or the common denominator in all patients irrespective of
what the contributing or risk factors are in each individual patient. Dr. Schwartz has not
only invested in ARKAY Therapeutics but also has joined the management team as the
Chief Medical Advisor. Robert Busch, MD, Albany Medical College, Albany, NY, a
renowned endocrinologist and a diabetes expert has graciously volunteered to be the
principal Investigator (PI) on the clinical study. Dr. Busch has served as a PI in over 40
clinical trials.
Ravi Kumar, Ph.D. the founder and CEO of ARKAY Therapeutics obtained M.S. and Ph.D.
in Molecular and Cell Biology from New York University. He has the subject matter
expertise in the metabolic, cardiovascular and chronic inflammatory disease space. Dr.
Kumar has over 30 years of academic and pharmaceutical industry experience which
includes The Cleveland Clinic Foundation, Pharmacia and Pfizer. He comes from a family
of diabetes patients, knows first-hand the limitations of the currently marketed treatment
options and the devastating consequences of diabetes-related complications.
The investment community, angel investors and venture capitalist firms alike are currently
focused so much on investing in the immuno-oncology space with a herd mentality and
have chosen to ignore the diabetes space. There are pharma companies and VC firms
who find ARKAY’s product concept “not innovative enough” because it is a combination
of repurposed pre-approved drugs. In the real-word, patients don’t care if the medicine
they are taking is innovative, new molecules or preapproved drugs; they just want a
sustainable and an affordable solution. Large pharma companies historically have used
at least $1B potential revenue threshold as a criterion to consider a new idea for a potential
investment or a partnership. The choice with TriGlytzaÔ is simple and straight forward:
an expensively priced innovative product developed from a NCE that can generate $1B
per year revenue for short term glycemic control with a small market share or a
competitively-priced patient-centric product that can provide sustained glycemic control
which can also generate equivalent or better revenue stream with a larger market share
with a positive impact on the lives of Type 2 diabetes patients worldwide. The 3-years
exclusivity from the 505(b)(2) regulatory strategy along with exclusivity from the issued
patent are expected to prevent competition from generic drugs until the patent expiration
in September 2034 which makes the revenue potential of TriGlytzaÔ comparable to a
drug developed from a NCE. In the prevailing environment, It has become increasingly

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difficult to raise capital for ARKAY’s clinical study to bring this very important patient-
centric product to the Type 2 diabetes patients. TriGlytzaÔ provides not only a superior
clinical solution but more importantly an affordable solution. Therefore, we are reaching
out to the global investment community to raise at least $10M for the human proof-of-
concept study with TriGlytzaÔ prototype. Multiple pharma companies in the diabetes
space have already expressed interest in partnering with ARKAY for the commercial
development after the completion of the human PoC study.
Conclusions
Pharmaceutical industry needs to explore Think-out-side-the-box approaches to address
the challenges of the real-world clinical practice: sustained glycemic control, preventing
clinical inertia, affordability and diabetes complications. It is now time for a paradigm shift
in the clinical management of Type 2 diabetes. Targeting the underlying pathophysiology
of multidimensional pro-inflammatory signaling cascade of events with a rationalized
combination product such as TriGlytzaÔ which is custom-designed to prevent beta cell
failure and decrease insulin resistance makes not only clinical sense and more importantly
an economic sense for Type 2 diabetes worldwide.
Please visit www.arkaytherapeutics.com for more information on the scientific rationale,
the product concept, the management team, board members and the scientific advisors.
Please contact ravi.kumar@arkaytherapeutics.com for the non-confidential business
plan.
Please feel free to share this article with your friends and family via LinkedIn and
other social media.
Glossary:
ADA: American Diabetes Association; AACE: American Association of Clinical
Endocrinologists; AngII: Angiotensin II; CARE: Clinical and Research Excellence; CDC:
Center for Disease Control; Cox-2: Cyclooxygenase-2; DPP-IV: Dipeptidyl Peptidase-IV;
EASD: European Association for the Study of Diabetes; FDA: Food and Drug Authority;
GLP-1: Glucagon-like Peptide-1; HbA1c: Hemoglobin A1c; IDF: International Diabetes
Federation; IL-1b: Interleukin-1b; NASH: Non-alcoholic Steatohepatitis; NFkB: Nuclear
Factor kB; PCOS: Polycystic Ovarian Syndrome; PGE2: Prostaglandin E2; PGH2:
Prostaglandin H2; PoC: Proof-of-concept; RAS: Renin-Angiotensin System; SGLT2:
Sodium Glucose Transporter-2; USPTO: United States Patent and Trademark Office
Key References:
Ballatori, P. et al. (2017) Diabetes and risk of cancer incidence: results from a population-
based cohort study in northern Italy. BMC Cancer 17(703): 1-8.
Cole, B.K. et. al (2010) Valsartan protects pancreatic islets and adipose tissue from the
inflammatory and metabolic consequences of a high-fat in mice. Hypertension 55: 715-
721.

11. 11
El-Bahrawy, H. et al. (2017) Targeting inflammation using celecoxib with glimepiride in the
treatment of obese type 2 diabetes Egyptian patients. Int J Diabetes Dev Ctries. 37(2):
97-102.
Fenske, R. et al. (2017) Prostaglandin E2 (PGE2) levels as a predictor for Type 2 diabetes
control in human subjects: A cross-sectional view of initial cohort study data. FASEB J.
Abstract No. 675.6
Fujita, H. et al (2007) Effect of cyclooxygenase-2 (COX-2) inhibitor treatment on glucose-
stimulated insulin secretion in C57BL/6 mice. Biochem. Biophys. Res. Commun. 363(1):
37-43.
Gonazalez-Ortiz, M. et al. (2005) Effect of Celecoxib, a Cyclooxygenase-2-specific
inhibitor, on insulin sensitivity, C-reactive protein, homocysteine, and metabolic profile in
overweight or obese subjects. Metab. Synd. Rel. Disord. 3(2): 95-101.
Goossens, G.H. et al. (2012) Valsartan improves adipose tissue function in humans with
impaired glucose metabolism: A randomized placebo-controlled double-blind trial. PLoS
One 7(6): e39930
IDF, International Diabetes Federation (2017) Facts and Figures. www.idf.org. Accessed
March 2, 2017.
Kandimalla, R. (2017) Is Alzheimer’s disease a Type 3 diabetes? A critical appraisal.
Biochim. Biophys. Acta. 1863(5): 1078-1089.
Kimple, M.E. et al. (2013) Prostaglandin E3 receptor, EP3, is induced in diabetic islets
and negatively regulated glucose and hormone-stimulated insulin secretion. Diabetes 62:
1904-1912.
Kumar, R. (2016) Anti-inflammatory-centric drug combination lowers non-fasting and
fasting blood glucose levels in C57BL/6 DIO mice with insulin resistance. Diabetes 65
(suppl. 1): A294.
Kumar, R. (2018) Evaluation of superiority of Valsartan+Celecoxib+Metformin over
Metformin alone in Type 2 diabetes patients (RESILIENCE). ClinicalTrials.gov Identifier:
NCT03686657.
Lu, C.H. et al. (2016) Additional Effect of Metformin and Celecoxib Against Lipid
dysregulation and Adipose Tissue Inflammation in High-fat Fed Rats with Insulin
Resistance and Fatty Liver. Eur. J. Pharmacol.
(2016). http://dx.doi.org/10.1016/j.ejphar.2016.07.012
Mendez-del vilar, M. et al. (2017) Effect of Diacerein as an add-on to metformin in patients
with type 2 diabetes mellitus and inadequate glycemic control. Arch. Endocrinol. Metab.
61(2): 188-192.

12. 12
Montvida, O. et al. (2018) Long-term trends in the antidiabetes drug usage in the U.S.:
Real-world evidence in patients newly diagnosed with Type 2 diabetes. Diabetes Care.
41(1): 69-78.
Okemah, J. et al. (2018) Addressing clinical inertia in Type 2 diabetes Mellitus: A review.
Adv. Ther. 35: 1735-1745.
Oshima, H. et al. (2006) Destruction of pancreatic b-cells by transgenic induction of
prostaglandin E2 in the islets. J. Biol. Chem. 281(39): 29330-29336.
Pscherer, S. et al. (2010) Effect of Renin-Angiotensin System blockade on insulin
resistance and inflammatory parameters in patients with impaired glucose tolerance.
Diabetes Care 33: 914-919.
Ramos-Zavala, M. et al. (2011) Effect of Diacerein on insulin secretion and metabolic
control in drug-naïve patients with type 2 diabetes. Diabetes Care, Published ahead of
print online on May 24, 2011.
Schwartz, S. et al. (2016) The time is right for a new classification system for diabetes:
Rationale and implications of the b-cell centric classification schema. Diabetes Care 39:
179-186.
Skyler, J.S. et al. (2017) Differentiation of diabetes by pathophysiology, natural history
and prognosis. Diabetes 66: 241-255.
Strain, W.D. et al. (2014) Clinical inertia in individualizing care for diabetes: is there time
to do more in type 2 diabetes? Diabetes Ther. 5(2): 347-354.
Van der Zijl, N.R. et al. (2011) Valsartan improves beta cell function and insulin sensitivity
in subjects with impaired glucose metabolism: a randomized control trial. Diabetes Care
34(4): 845-851.
Vinik, A.I. (2004) Inflammation: The root of all evil in diabetes and the dysmetabolic
syndrome. Medscape http://www.medscape.com/reviewarticle/496269.
Zhao, X-B. et al (2016) Diabetes mellitus and prognosis in women with breast cancer. A
systematic review and meta-analysis. Medicine 95(49): 1-7.