This document discusses the management of diabesity, which is defined as a combination of type 2 diabetes and obesity. It outlines strategies for managing diabesity, including non-pharmacological therapies like physical activity and nutrition. Various drug therapies are discussed, including their effects on weight. Glucagon-like peptide 1 agonists and SGLT2 inhibitors can help with weight loss. Insulin therapies vary in their effects, with some newer insulins being weight-neutral. Bariatric surgery is an option for selected resistant cases seeking glycemic control and weight loss. The overall aim of management is achieving glucose control while reaching an optimal weight.

1. Management
of
Diabesity
BY
TAREK AL AREENY , MD
ASSOCIATE PROFESSOR OF
PREVENTIVE MEDICINE
TAREK1.MOHAMED@MU.EDU.EG
00201002416891

2. Tarek1.mohamed@mu.edu.eg

3. Presentation outlines
Introduction, definition & burden of diabesity
Diabetes & Obesity “ double burden ”
Strategies in managing diabesity
Non Insulin “Oral and Injectable Therapies”
 Insulins & Diabesity
 Role of Bariatric Surgery in diabesity
Take home messages
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4. Introduction :
 A new word, “diabesity,”
describes a continuum of
metabolic imbalance and
disease that ranges all the
way from mild blood-
sugar imbalance to insulin
resistance to full-blown
diabetes.
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5. Diabesity or Metabolic syndrome?!
Diabesity is defined as a
combination of type-2
diabetes and obesity, with or
without associated risk factors
such as dyslipidemia and
hypertension.
Thus diabesity forms a subset
of metabolic syndrome.
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6. So, if your patient have obesity and type 2 diabetes,
you can diagnose him as having diabesity.
But he doesn’t have to be a diabetic – or even have
symptoms – to be suffering from diabesity especially
its early stages .
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7. Burden of Diabesity:
 Diabesity is a leading cause of
most chronic disease in the 21st
century.
 Specifically, those with diabesity
are at an increased risk of heart
disease, stroke, dementia, cancer,
high blood pressure, blindness
and renal failure.
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8. Diabetes and obesity
The link between type 2 diabetes and obesity has been
recognized for decades with the risk of developing type 2
diabetes increasing progressively with the amount of
excess weight.
The likelihood of developing type 2 diabetes in
overweight people is increased eight-fold and in obese
people increased 40-fold.
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9. Diabetes and obesity
 Type 2 diabetes results from a combination of
abnormal insulin secretion and insulin resistance in
over-weight people, which are compounded by
excessive caloric intake and a sedentary lifestyle
 Excessive fat stores are an important cause of
increased free fatty acid and triglyceride in skeletal
muscle , influencing insulin resistance .
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10. Diabetes and obesity
 what makes the condition more worse is rising
blood glucose levels and decreased insulin action
leads to an accelerated rate of lipolysis (fat
breakdown) further leading to insulin resistance
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11. Why obesity hinders diabetes control
and increase mortality ?
 Increase insulin resistance & glucose intolerance
 Exacerbating other metabolic complications such as
hypertension and dyslipidemia
 Regarding mortality, compared with normal weight
individuals with diabetes, the mortality rate is 2.5-3.3 times
higher in diabetics with body weights that are 20-30% above
their ideal weight and 5.2-7.9 times higher in those with
body weights 40% above ideal weight
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12. Why obesity hinders diabetes control
and increase mortality ?
 The proposed mechanism of this increased mortality in obese
diabetics may be due to excess body fat, particularly abdominal
fat, along with the presence of insulin resistance leads to a Pro-
Atherogenic lipid profile with high triglyceride and
apolipoprotein b concentrations, an increased proportion of small
dense LDL particles, and a reduced concentration of HDL
cholesterol.
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13. Why obesity hinders diabetes control
and increase mortality ?
 This Pro-Atherogeinc factor,
along with a pro-thrombotic
and a pro-inflammatory
profile significantly worsens
an individual’s risk of
cardiovascular disease and
overall mortality.
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14. Where is the
challenge in
dealing with
diabesity?
For most people , neither dieting nor current
pharmacological interventions are effective
in achieving long-term weight reduction .
So, nowadays , reducing the rate of
diabesity is a multi-task operation , involving
dietary, exercise and lifestyle counselling
alongside the medical management of
diabetes and obesity related health risks
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15. Strategies in
managing
diabesity
The management of
diabetes and obesity
has been discussed in
detail elsewhere.
This presentation aims
to highlight :
I) important effects
of diabetes therapy
on obesity
II) obesity treatment on
diabetes, as well as impact of
these treatments on
dyslipidemia and
hypertension.
• III) Important drug-drug
interactions are also
discussed.
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16. Strategies in managing diabesity
 The earlier glucocentric approach in the
management of diabetes is now being replaced
by an aim to achieve composite targets, i.e.,
glucose reduction, and weight reduction, without
hypoglycemia.
 Attention is also being paid to the pleiotropic
effects of anti-diabetic medication, e.g., lipid
lowering and blood pressure lowering effects,
which mediate improvement in cardiovascular
outcomes.
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17. Non Pharmacological Therapy
 Nonpharmacological therapy, namely physical
activity, cessation of smoking, and medical nutrition
therapy are important aspects of therapy in diabesity.
 Weight reduction is a central pillar of management.
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18. Value of weight reduction in diabesity
management
 Weight reduction improves insulin sensitivity, and reduces lipid levels.
 In the person with diabetes, excess dietary fat is converted to adipose tissue
faster than dietary carbohydrate.
 Also, fat-diet-induced thermogenesis is less with a fat-rich diet than with a
carbohydrate or protein rich diet.
 Therefore, calorie redistribution, apart from calorie restriction, is an
important part of nutritional therapy in diabesity.
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19. Physical Activity
 At least 30 minutes of moderate intensity physical activity every
alternate day is recommended to improve insulin sensitivity and reduce
weight.
 Resistance exercises of similar duration, twice a week, should also be
performed.
 Folk dances, belly dancing , Zumba dancing should be promoted as
acceptable, low cost, indigenous forms of healthy exercise.
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23. Non Insulin
“Oral and
Injectable
Therapies” :
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24. Non Insulin “Oral and Injectable Therapies”
 Weight gain is considered an inevitable part of good glycemic control
using conventional modalities of treatment.
 Institution of glucose lowering therapy may lead to weight gain by
correcting glycosuria, and reducing this drainage of calories
 Some drugs, however, are linked with a specific propensity to gain
weight. Pioglitazone, for example, should be used in lowest effective
doses.
 Other drugs such as gliptins “ such as alogliptin … are weight-
neutral.
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25. Oral Drug Therapy
 Sulfonylurea use is linked to significant weight gain.
 Addition of sulfonylureas to metformin is also associated with
weight gain, but to a lesser degree, according to meta-analysis.
 A meta-analysis has shown that a combination of sulfonylureas
and insulin does not lead to weight gain.
 Alpha-glucosidase inhibitors have an insignificant effect on
weight, as per a meta-analysis of 41 studies.
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26. Oral Drug Therapy
 Metformin is reported to have a
beneficial effect on body weight by
some, but not all, researchers.
 Metformin has been shown to reduce
weight, as compared with
sulfonylureas, in meta-analysis.
 Metformin, when used as co-therapy,
also mitigates the weight gain seen
with sulfonylureas and repaglinide.
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27. Glucagon-like peptide 1 ( GLP1) agonists &
Diabesity :
 The glucagon-like peptide1 (GLP1) agonists, liraglutide, lixsenatide, and
exenatide, are linked with weight loss.
 Mechanisms :
I) central hypothalamic effect, by reducing appetite.
II) slowing gastric emptying.
III) effects on fatty acid metabolism.
This composite benefit of achieving euglycemia without weight gain and
hypoglycemia makes GLP1 analogues preferred drugs for diabesity.
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28. SGLT2 Inhibitor & Diabesity
 Sodium-glucose cotransporter (SGLT) 2
inhibitors increase urinary glucose excretion
by inhibiting renal glucose reabsorption,
thereby having subsequent anti-hyperglycemic
effects and reducing body weight.
 SGLT2 inhibitor namely, empagliflozin
increases fat utilization and browning in white
adipose tissue and attenuates obesity-induced
inflammation and insulin resistance by
activating M2 macrophages.Tarek1.mohamed@mu.edu.eg

29. SGLT2 Inhibitor & Diabesity
 Nowadays , SGLT2 application in the treatment of obesity in diabetes is
extensive.
 Although current guidelines do not recommend their use over metformin in
certain situations, SGLT2 inhibitors lead to a modest reduction is body
weight.
 Given the remarkable effect on weight loss the combination therapy of
SGLT2i and anorectics such as “phentermine” offers, SGLT2 relevance in
treatment of individuals with obesity and diabetes is likely to magnify if
similar results are replicated in individuals with diabetes.Tarek1.mohamed@mu.edu.eg

30. SGLT2 Inhibitor & Diabesity
 Practice Pearls:
 On average, SGLT2 inhibitors lead to weight loss of ~2 kilograms.
 SGLT2 inhibitors’ weight loss is limited if there is a compensatory increase
in food intake by an individual.
 Combination therapy with SGLT2 inhibitors and anorexiogenic drugs may
prove effective for weight loss in diabetes, however, future studies are
needed to establish the benefit.
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31. Last word in non insulin therapy for
Diabesity
 Following the AACE guidelines, individuals in need of a combination
antihyperglycemic therapy and who wish to lose weight are usually treated
with metformin and an SGLT2 i or a GLP-1 agonist.
 Data supporting the combination therapy with all three medication classes is
limited. On the other hand, there have been studies conducted that endorse
the use of dual-therapy with SGLT2i and GLP-1 agonists.
 More specifically, a combination study with exenatide and dapagliflozin
therapy is advantageous because it leads to an average weight loss of 3.4 kg.
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32. Insulins & Diabesity
Insulin is an essential molecule in the management of diabetes.
Traditionally, insulin use is thought to be associated with weight gain.
Newer insulins such as insulin detemir, however, tend to reduce
weight while providing glycemic control. This pharmacological effect
may be mediated by a central hypothalamic effect, or by avoidance of
defensive snacking which occurs in response to hypoglycemia.
Glargine insulin and NPH insulin use is linked with weight gain.
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33. Insulins & Diabesity
 Use of metformin, and weight-sparing insulin analogues such as insulin
detemir, should be encouraged as monotherapy, or in combination with
other drugs, in diabesity.
 In type 2, the addition of SGLT2 inhibitors to insulin may improve
glycemic control, lessen the amount of insulin needed, and alleviate the
insulin-related weight gain. Nonetheless, current guidelines support the
addition of metformin, not an SGLT2 inhibitor, to insulin in individuals
whose glycemic levels are not controlled despite proper insulin use.
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34. Insulins & Diabesity
 While there was some appeal in utilizing SGLT2 inhibitors in the
treatment of type 1 diabetes to control the weight gain commonly
seen in this population, the advantage was short lived due to the
exposure of ketoacidosis risk seen with SGLT2i use.
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35. Role of Bariatric Surgery in diabesity :
 Bariatric surgery is an emerging field in
the management of diabesity.
 Weight reduction surgery includes
restrictive procedures (laparoscopic
banding, gastroplasty) and procedures
which combine mal-absorptive with
restrictive operations (Roux-en-Y gastric
bypass, duodenal switch procedure,
biliopancreatic diversion).
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36. Role of Bariatric Surgery in diabesity :
 These surgical procedures have been hailed as a ‘cure’ for both
diabetes and obesity.
 However, such surgery is associated with multiple metabolic and
endocrine disorders and used only in selected, resistant cases.
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37. Take home messages
 Management strategies of diabesity should be geared
towards achieving glycemic control, while simultaneously
reaching optimal weight in diabesity.
 Appropriate methods of management, using dietary therapy,
physical activity, metformin, newer insulin analogues such as
detemir, SGLT2 and GLP-1 analogues, must be promoted.
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