Abordaje terapeutico del paciente
con diabetes y obesidad
Barto Burguera MD, PhDProfessor of Medicine Director of Obesity ProgramsEndocrinology and Bariatric InstitutesCleveland Clinic Lerner College of Medicine of [email protected]
Learning Objectives
Obesity: severity of the problem
Weight gain and development of diabetes
Therapeutic tools to treat Obesity
Weight loss as therapeutic tool to treat diabetes
Retinopathy
Neuropathy
Nephropathy
CAD
Diabetes
Obeso
Diabetes
Hypertension
Dislipemia
CAD
International Diabetes Federation, 2003.NAASO. Arch Intern Med 2000;160:898–904Ng M. et al Lancet Published online May 29, 2014
• In Western countries, nearly 90% of T2DM cases can be attributed to weight gain
• Two-thirds of adults diagnosed with T2D have a BMI of ≥27 kg/m2
Medical Complications of Obesity
Phlebitisvenous stasis
Coronary heart disease
Pulmonary diseaseabnormal functionobstructive sleep apneahypoventilation syndrome
Gallstones
Gout
Diabetes
Osteoarthritis
Fatty liver diseasesteatosissteatohepatitiscirrhosis
Hypertension
Dyslipidemia
Cataracts
Skin disorders
Pancreatitis
Intracranial hypertensionCognitive dysfunction
Cancerbreast, uterus, cervix, ovary, prostate, kidney, colon, Esophagus, pancreas, gallbladder, liver
Gynecologic abnormalitiesabnormal mensesinfertilitypolycystic ovarian syndrome
Stroke
Patients are concerned about weight gain: questions posted on diabetes web forums
• “I’ve heard that once you control blood sugar you gain weight?”
• “Is it true that insulin causes weight gain? I would have hoped to lose weight”
• “Since starting on insulin 8 months ago, I’ve gained 26 kg. I am so depressed. Are there other treatments I could try instead?”
• “I’ve tried hard to lose weight, but since starting insulin my weight has increased. I’m willing to be more strict with my diet but I worry that could cause hypoglycaemia….”
• “Are there any drugs for weight loss suitable for diabetics on insulin?
Key challenges of type 2 diabetes
1. Diabetes is a progressive disease characterized by:
– Declining beta-cell function– Deterioration of glycemic control– Microvascular complications– Increased risk of cardiovascular disease
1. As diabetes treatments are added to control glucose, physicians and patients frequently need to deal with:
– Increased risk of hypoglycaemia– Weight gain– Complex treatment regimens– Increased requirement for self monitoring
Is there any benefit for weight loss in T2DM?
Modest Weight Loss Has Benefits, with Greater Weight Loss Associated with Greater Benefit
• Measures of glycemia1
• Triglycerides1 and HDL cholesterol1
• Systolic and diastolic blood pressure• Hepatic steatosis measured by MRS2
• Measures of feeling and function:– Symptoms of urinary stress incontinence5
– Measures of sexual function6,7
– Quality of life measures (IWQOL)8
• NASH Activity Score measured on biopsy3
• Apnea-hypopnea index4
• Reduction in CV events, mortality, remission T2DM9
1. Wing et al. Diabetes Care 2011;34:1481-14862. Lazo et al. Diabetes Care 2010;33:2156–21633. Promrat et al. Hepatology 2010;51:121–1294. Foster et al. Arch Intern Med 2009;169:1619–1626
5. Phelan et al. Urol. 2012;187:939-944 6. Wing et al. Diab Care 2013;36:2937-29447. Wing et al. Journal of Sexual Medicine 2010 ; 7:156-658. Crosby, Manual for the IWQOL-LITE Measure9. Eliasson B, Lancet Diabetes Endocrinol 2015;3(11): 847–54.
-3.0%
-5.0%
-10.0%
-15.0%
ObesityPrimary Problem
Medications
Diabetes Treatment
•Lifestyle Modification
•Drug Therapy:
– >85% suffer obesity
– Obesity treatment useful approach?
HISTORY OF PRESENT ILLNESS:
• Mary K is a 48 year old female who is presenting on July 16, 2015 for weight management
• History of bipolar disorder x 19 years.
• History of obesity. Since age 18. Pretty much overweight since high school
– Portion sizes, medications, eating too much fat and sugar, emotional eating and lack of physical activity have been major
continuing factors to her weight gain
• Hx of prediabetes x 1 year. Currently treated with life style intervention and metformin 500 mg bid.
• She did not tolerate higher doses due to GI side effects
• Monitors her BG qw. Glucose readings in AM~ 110s w/o evidence of hypoglycemias
• Glucose control has slowly deteriorated over the last few months; hemoglobin A1c increased from 5.8 6.1%
• 10 pound weight loss
• Taking several medications associated to weight gain such as Latuda, Lithium, neurontin and trazodone.
History
• Diet: Her breakfast consists of hot cereal or Greek yogurt or shake with fruits and spinach
• Lunch she has several slices bread with ham and cheese and mayonnaise or a homemade turkey
• Dinner she usually has chicken, spinach salad and a small potato
• She drinks water and coffee.
• Her level of physical activity is limited: she walks once a week for a period of 20 minutes
• Her appetite is not well controlled. She is pretty much hungry all the time
• She does not sleep well usually less than 7 hours. There is no evidence of obstructive sleep apnea
• Her level of stress is 6/10. She is frustrated/depressed with her weight and her general health status
REVIEW OF SYSTEMS:
• WEIGHT: decreased 10 lb.
• Fatigue.
• EYES: Normal
• HYDRATION: no thirst and polydipsia.
• CARDIAC: no chest pain, dyspnea, palpitations or edema
• GI: no nausea, fullness, vomiting, diarrhea, constipation, GI bleeding or heartburn
• GU: nocturia
• SEXUAL/REPRODUCTIVE: normal. IUD.
• SKIN: normal
• MUSCULO-SKELETAL: Joint pain both knee(s) and Back pain.
• NERVOUS SYSTEM: no numbness, paresthesias, weakness, cramping, burning or dizziness
• PSYCH: depression. History of bipolar disorder. History of alcohol abuse in the past.
PAST MEDICAL HISTORY
• Bipolar Affective (Hcc) - 1988
• Psoriasis - 1989
• Psoriatic Arthritis (Hcc) - 1992
• Stiff-Man Syndrome - 2008
• Plantar Fasciitis
• Alcohol Dependence, in Remission
• Asthma
• Allergic Rhinitis, Cause Unspecified (Allergic rhinitis)
• Hepatitis (nonspecific)
• Lower Leg Dvt (Deep Venous Thrombosis) (Hcc) - 2004 (one in each leg)
• Tendonitis of Ankle - 7/17/2013
• History of prediabetes
• Hx of hypothyroidism.
• Morbid Obesity
Results for as of 7/18/2015 10:29AM
Ref. Range 11/20/2014 15:18 1/8/2015 15:18 6/12/2015 12:49
• Hemoglobin A1C Latest Range: 4.0-6.0 % 5.8 6.1 (H)
• Free T4 Latest Range: 0.7-1.8 ng/dL 1.3
• TSH Latest Range: 0.400-5.500 uU/mL 2.820
• Vitamin D 25 Hydroxy Latest Range: 31.0-80.0 ng/mL 22.1 (L)
SOCIAL HISTORY
• Lives in a nursing home. Her mother is here with her today
• Employer And Job Title: No employer specified (nanny)
• Years Of Education Completed: 14 years
• Marital Status: Unknown with no children
• Tobacco Use: 1 packs/day, for 30 years. Quit 01/01/2008. Types: Cigarettes
• Alcohol Use: No (sober 9 years)
• Drug Use: No (quit years ago "everything but crack and heroin")
• Sexual Activity: Patient is not presently sexually active.
Current outpatient prescriptions:
• loratadine (CLARITIN) 10 mg tablet Take 1 tablet by mouth once daily.
• gabapentin (NEURONTIN) 300 mg capsule 300 mg in am and pm, 600 mg at night (total daily 1200)
• Metformin (glucophage) 500 mg tablet Take 1 tablet by mouth once a daily.
• blood sugar diagnostic (ACCU-CHEK SMARTVIEW TEST STRIP) test strip Daily or Use as instructed
• Lancets (ACCU-CHEK FASTCLIX) lancets Daily or Use as instructed
• apremilast (OTEZLA) 30 mg tablet Take 30 mg by mouth twice daily.
• traZODone (DESYREL) 100 mg tablet Take 100 mg by mouth daily at bedtime.
• levothyroxine (SYNTHROID) 88 mcg tablet Take 1 tablet by mouth daily before breakfast.
• topiramate (TOPAMAX) 100 mg tablet Take 100 mg by mouth once daily.
• LAMOTRIGINE 200 mg tablet Take 200 mg by mouth once daily.
• lurasidone (LATUDA) 80 mg ORAL tablet Take 80 mg by mouth once daily.
• lithium CR 450 mg ORAL CR tablet Take 1 tablet by mouth twice daily.
PHYSICAL EXAM:
• BP 155/84 | Pulse 71 | Ht 157.5 cm (5' 2") | Wt 104.101 kg (229 lb 8 oz)
• Body mass index is 41.97 kg/(m^2).
• Appearance Well appearing, alert, in no acute distress, well-hydrated, well nourished., obese
• Eyes PERRLA, conjunctiva and sclera normal
• Neck Supple, no adenopathy; thyroid symmetric, normal size, no bruits
• Heart RRR with normal S1 and S2, no murmurs, no gallops, no JVD appreciated
• Lungs clear to auscultation
• Abd bowel sounds normoactive, no bruits, soft, non-tender, non-distended, without organomegaly
• Extremities Normal, No deformities, No skin discoloration, No edema and Normal pulses bilaterally.
• Feet: No foot lesion
• Neuro Awake, alert and oriented x 3, No involuntary motions. and Reflexes symmetrical
• Skin Color, texture, turgor normal. No rashes or lesions
Impression and plan: Mary K is a very pleasant 48 year old female with hx of:
Impression and plan: Mary K is a very pleasant 48 y.o. female with hx of:
1.- Prediabetes for the last year. She is not compliant
It is going to get worse
• Her HgA1c is at 6.1%.
• Suboptimal eating habits (Nursing home)
• Limited exercise
• Poor sleeping higiene
• Follow-up with endocrine.
• Add SU, DDP4-inh or Glitazone for the time being?
2.- Morbid obesity. This patient's BMI is 42.
• Referral to the bariatric Institute ASAP.
3.- History of bipolar disease: follow-up with psychiatry.
4.- Stiff man syndrome. Follow up with neurology.
Follow-up in 6 months.
Dietician.
Level 4.
Impression and plan: Mary Lou is a very pleasant 48 years old y.o.
female with hx of:
1.- Prediabetes for the last year. She is not compliant
• It s going to get worse
• Her HgA1c is at 6.1%.
• Suboptimal eating habits (Nursing home)
• Limited exercise
• Poor sleeping higiene
• Follow-up with endocrine.
• Add SU or Glitazone for the time being?
2.- Morbid obesity. This patient's BMI is 42.
• Referral to the bariatric Institute ASAP.
3.- History of bipolar disease: follow-up with
psychiatry.
4.- stiff man syndrome. Follow up with neurology.
Follow-up in 6 months.
Dietician.
Level 4.
1.- Morbid obesity. This patient's BMI is 42.
• Starting on lifestyle intervention program involving improvement of diet, a personalized
exercise program and the possibility of using medications to control her appetite
• She will also follow-up with dietitian
• Exercise program
• We need to control her appetite
• Consider starting appetite suppressants
2.- History of bipolar disease: follow-up with psychiatry
• Topamax as per her neurologist Some of the other antipsychotics that she is taking
increased appetite.
• Talk to her psychiatrist regarding anti-psych meds
3.- Prediabetes for the last year.
• Her HgA1c is at 6.1%. Aggressive LSI will prevent development of diabetes
• She is willing to try to walk 20 min bid. -> Exercise Physiologist
• She should monitor her BG qw. F/u Ophthalm f/u q/yr
• We will also check HgA1c in 3 months.
• Not tolerating metformin GLP-1 analog (or sGLUT-2 inh)– Vicotza 0.6 mg 1.8 mg sc qd
• RTC in 1 month after above consults obtained
• Level 5
Follow-up when we treat the Diabetes
1.- Prediabetes for the last year. She is more compliant.
Patient is being followed by endocrinology
She stopped taking metformin GI SE
Started on Amaryl 2 md bid
• Her HgA1c is at 6.1% 5.9%.
2.- Morbid obesity. This patient's BMI is 42 44
Patient was not a good surgical candidate due to her bipolar disease
3.- History of bipolar disease: follow-up with psychiatry
4.- Stiff man syndrome. Follow up with neurology
Follow-up in 6 months PRN
Patient stopped taking metformin GI SE and started on Amaryl 2 md bid
Patient continues to be frustrated. Psychiatry follow-up.
Continues to eat poorly and she does not exercise.
She has developed obstructive sleep apnea problems with C-pap
Increased joint pain
Follow-up: when we treat the Obesity
• .- DMT2 for the last year. She is more compliant.
• Patient is being followed by endocrinology.
She stop taking metformin GI SE
Started on Amaryl 2 md bid
• Her HgA1c is at 6.4% 5.9%.
• Continues to eat poorly and she does not
exercise.
• Poor sleeping higiene
• 2.- Morbid obesity. This patient's BMI is 42 44.
• Patient was not a good surgical candidate due to
her bipolar disease.
• 3.- History of bipolar disease: follow-up with
psychiatry.
• 4.- stiff man syndrome. Follow up with neurology.
• Follow-up in 6 months PRN.
• 1.- Morbid obesity. This patient's BMI was 42
• Lifestyle intervention program: improvement of diet, exercise program
• Exercise program
• Follow-up with dietitian
• Medications to reduce appetite
• On Topamax as per her neurologist.
2.- History of bipolar disease: follow-up with psychiatry
• Off Trazadone and Latuda. Cont. with Lithium
• Started on Wellbutrin. Close f/u by Psych
• 2.- Prediabetes for the last year.
• HgA1c is at 6.1%. 5.9%
• Walking 60 min qd. -> Exercise Physiologist
• Victoza 1.8 mg sc qd
• She should monitor her BG bid. F/u Ophthalm f/u q/yr.
• We will also check HgA1c in 2 months.
This patient's BMI was 42 29.7
(14 months later)
Patient is taking metformin 500 mg after dinner.
Victoza 1.8 mg subcutaneous once a day.
Exercise program. Follow-up with dietitian.
On Topamax as per her neurologist.
Off Trazadone and Latuda. Cont. with Lithium. Wellbutrin recently added.
Close f/u with psychiatry and psychology.
Follow up.
50 year old female who originally presented on July 16, 2015 for diabetes
management and today she is here for follow-up. (1-17-2017)
In our first visit we outlined a lifestyle intervention program involving a personalized dietary program, we optimized her level of
physical activity, provide her with an exercise program and optimized her T2D therapy
• She is happy with the progress obtained over the last few weeks
• Aerobic exercising 4-5 days per week. Water exercises and weights
• She is having problems with her nutrition at her nursing home Eating more carbs over the holidays
• She does not sleep well usually less than 7 hours. There is no evidence of obstructive sleep apnea.
• She is very proud of her accomplishment. She has lost 85 pounds
• History of type 2 diabetes and we have treated her with metformin 500 mg bid and also Victoza 1.8 mg sc once a day.
• In spite of that weight loss and surprisingly her hemoglobin A1c has increased up to 12.7% (10.1---> 7.2%-->12.7).
• Given this circumstance she was started on Lantus 10 un by her PCP. She did not tolerate Invokana due to vaginal yeast
infection.
• Her blood sugars have been in the 150s-240. The blood glucose readings are getting better now that she has become more
physically active.
Mary Kay is a very pleasant 50 year old yo female with hx of:
Impression and plan:
1.- DMT2 for the last year. Her metabolic profile has significantly improved with weight loss
Her HgA1c was at 10.7--> 7.3-->12.3%.
She will continue with swimming pool twice a week and also walk on a daily basis
She will continue with Victoza at a dose of 1.8 mg and 500 mg of metformin bid
She will increase Lantus to 14 un.
Letter to NH asking for a low carb diet
She did not tolerate Invokana 100 mg qd.
She needs Ophthalm f/u q/yr.
We will also check HgA1c in 3 months.
2.- Morbid obesity. This patient's BMI is 42-->39-->37.8.-->36.8-->35-->33.1--> 30.3. Patient has responded extremely well to a lifestyle
intervention program involving improvement of her diet, a personalized exercise program
She seems to be doing quite well with Victoza.
Very important that she continues with an exercise program. She will also follow-up with dietitian.
She should continue to take Topamax as per her neurologist which is associated with decreased appetite.
History of bipolar disease. She is being followed by psychiatry. She has been able to taper the much all her medications. She is back on
Latuda.
Next visit in 12 week(s).
• This nice lady has a history of T2D and we have treated her with
– Metformin 500 mg bid
– Victoza 1.8 mg subcutaneous once a day
– Lantus 12 u qhs. She is doing very well. She has lost 85 pounds.
• In spite of that weight loss and surprisingly her hemoglobin A1c
had increased up to 12.7%
• Eating much healthier at the NH and more active
• HgA1c has significantly reduced to almost normal (10.1--->
7.2%-->12.7--> 7.4% today
Follow up.
50 year old female who originally presented on July 16, 2015 for
diabetes management and today she is here for follow-up. (4-11-2017)
• Impression and plan:
• Mary Kay Moore is a very pleasant 50 year old yo female with hx of:
• 1.- DMT2 for the last year. Her metabolic profile has significantly improved with weight loss
• Her HgA1c was at 10.7--> 7.3-->12.3--> 7.4%.
• She will continue with swimming pool twice a week and also walk on a daily basis
• She will continue with Victoza at a dose of 1.8 mg and try to increase to 1000 mg of metformin twice a day.
• She will reduce Lantus to 12 un.
• 2.- Morbid obesity. This patient's BMI is 42-->39-->37.8.-->36.8-->35-->33.1--> 29.5
• Patient has responded extremely well to a lifestyle intervention program involving improvement of her diet, a personalized exercise program and medications to
control her appetite. She seems to be doing quite well with Victoza.
• Very important that she continues with an exercise program. She will also follow-up with dietitian.
• She should continue to take Topamax as per her neurologist which is associated with decreased appetite.
• History of bipolar disease. She is being followed by psychiatry.
• Next visit in 12 week(s).
A1C 6.5 – 7.5%**
Monotherapy
MET +
GLP-1 or DPP4 1
TZD 2
Glinide or SU 5
TZD + GLP-1 or DPP4 1
MET +Colesevelam
AGI 3
2 - 3 Mos.***
2 - 3 Mos.***
2 - 3 Mos.***
Dual Therapy
MET +
GLP-1 or
DPP4 1+
TZD 2
Glinide or SU 4,7
A1C > 9.0%
No Symptoms
Drug Naive Under Treatment
INSULIN
± Other
Agent(s) 6
Symptoms
INSULIN
± Other
Agent(s) 6
INSULIN
± Other
Agent(s) 6
Triple Therapy
AACE/ACE Algorithm for Glycemic
Control Committee
Cochairpersons:
Helena W. Rodbard, MD, FACP, MACE
Paul S. Jellinger, MD, MACE
Zachary T. Bloomgarden, MD, FACE
Jaime A. Davidson, MD, FACP, MACE
Daniel Einhorn, MD, FACP, FACE
Alan J. Garber, MD, PhD, FACE
James R. Gavin III, MD, PhD
George Grunberger, MD, FACP, FACE
Yehuda Handelsman, MD, FACP, FACE
Edward S. Horton, MD, FACE
Harold Lebovitz, MD, FACE
Philip Levy, MD, MACE
Etie S. Moghissi, MD, FACP, FACE
Stanley S. Schwartz, MD, FACE
* May not be appropriate for all patients
** For patients with diabetes and A1C < 6.5%, pharmacologic Rx may be considered
*** If A1C goal not achieved safely
† Preferred initial agent
1 DPP4 if PPG and FPG or GLP-1 if PPG
2 TZD if metabolic syndrome and/or
nonalcoholic fatty liver disease (NAFLD)
3 AGI if PPG
4 Glinide if PPG or SU if FPG
5 Low-dose secretagogue recommended
6 a) Discontinue insulin secretagogue
with multidose insulin b) Can use pramlintide with prandial insulin
7 Decrease secretagogue by 50% when added to GLP-1 or DPP-4
8 If A1C < 8.5%, combination Rx with agents
that cause hypoglycemia should be used with caution
9 If A1C > 8.5%, in patients on Dual Therapy,
insulin should be considered
MET +
GLP-1
or DPP4 1 ± SU 7
TZD 2
GLP-1
or DPP4 1± TZD 2
A1C 7.6 – 9.0%
Dual Therapy 8
2 - 3 Mos.***
2 - 3 Mos.***
Triple Therapy 9
INSULIN
± Other
Agent(s) 6
MET +
GLP-1 or DPP4 1
or TZD 2
SU or Glinide 4,5
MET +
GLP-1
or DPP4 1+ TZD 2
GLP-1
or DPP4 1 + SU 7
TZD 2
MET † DPP4 1 GLP-1 TZD 2 AGI 3
Available at www.aace.com/pub
© AACE December 2009 Update. May not be reproduced in any form without express written permission from AACE
• Foto DC
48 y.o. patient: CC obesity and diabetes
• Obese “all his life”
• Multiple diets and weight-loss programs: PSMF, WW, …
– Weight regained
• Very little exercise due to knee pain and “lack of time”
• Always tired and almost fell asleep on his job
• Anesthesiologist
• Stressful schedule
• Night shift. Poor sleeping
• He skips meals frequently: snacking
• Meds: Omeprazol
• Insulin Lantus 10 un AM, Novolog 10 un tid, Actos 30 mg.
• Atenolol 50 mg
• Simvastatin: 40 mg, Ezetimibe 10mg
• Adiro 100 mg, Prozac 20 mg
• Weight: 120.4 kg (265 lb) ht: 175.3 cm (5' 9") BMI: 39.2 kg/m2
Waist: 130 cm (51”) BP: 145/95 mm hg. Pulse: 80
• PE:
– Acanthosis nigricans. No goiter
– Abd: Striae < 1cm. Trace edema
WEIGHT GAIN ASSOCIATED WITH USE ALTERNATIVES(WEIGHT REDUCING IN
PARENTHESES)*
Insulin (weight gain differs with type and regimen used)
Sulfonylureas Thiazolidinediones Sitagliptin? Metiglinide
(Metformin) (Acarbose) (Miglitol) (Pramlintide) (Exenatide) (Liraglutide)(sGLT-2 inh).
Medications for Diabetes and Weight
Apovian CM, Aronne LJ, Bessesen DH et al. Pharmacologic Management of obesity: An Endocrine Society clinical practice guideline. J Clin Endocrinol Metab 2015 doi:10.1210/jc.2014-3415
* Only liraglutide 3.0 is FDA-approved for chronic weight management in patients with BMI 30+ kg/m2 or BMI 27 <30 kg/m2 with one or more comorbidities.
Diabetes therapy:
Glucocentric VS.
• Pt with T2DM.
– Obesity is a complication
Adipocentric
• Pt with Obesity and comorbidities:
– T2DM
– HTA
– OA
– OSA
– GERD
– Fatty Liver
Diabetes therapy:
Glucocentric VS.
• Pt with T2DM. Obesity complication
• Therapeutic target: HgA1c
Adipocentric
• Pt with Obesity and comorb:T2DM
47
Glucose control gets worse overtime
UKPDS 34. Lancet 1998:352:854–865; Kahn et al, (ADOPT), NEJM 2006;355(23):2427-43
6.2% – upper limit of normal range
8.0
6.0
7.5
7.0
6.5
Time (years)
0
0 2 3 4 51
Rosiglitazone vs Metformin–0.13 (–0.22 to –0.05), P=0.002
Rosiglitazone vs Glibenclamide–0.42 (–0.50 to –0.33), P<0.001
ADOPT
6
7
8
9
Med
ian
Hb
A1
c(%
)
Years from randomization
Conventional*
GlibenclamideMetforminInsulin
Recommended treatment
target ≤7.0†
2 4 6 8 100
UKPDS
7.5
8.5
6.5
*Diet initially then sulphonylureas, insulin and/or metformin if FPG > 15 mmol/l
†ADA clinical practice recommendations. n=5102
Metformin
Glibenclamide
Rosiglitazone
Diabetes therapy:
Glucocentric VS.
• Pt with T2DM. Obesity complication
• Therapeutic target: HgA1c
Adipocentric
• Pt with Obesity and comorb:T2DM
• Therapeutic target: BMI, abd. cc
Diabetes therapy:
Glucocentric VS.
• Pt with T2DM. Obesity complication
• Therapeutic target HgA1c
• Most common therapies
Weight gain
• Based on UKPDS data
Adipocentric
• Pt with Obesity and comorb:T2DM
• Therapeutic target: BMI, abd. Cc
Most therapies result in weight gain over time
Glibenclamide (n=277)
Years from randomisation
Insulin (n=409)
Metformin (n=342)
Conventional treatment (n=411); diet initially then sulphonylureas, insulin and/or metformin if FPG >15 mmol/L
UKPDS: up to 8 kg in 12 years ADOPT: up to 4.8 kg in 5 years
Weig
ht
(kg)
Rosiglitazone, 0.7 (0.6 to 0.8)Metformin, -0.3 (-0.4 to -0.2)**Glibenclamide, -0.2 (-0.3 to 0.0)**
Change in w
eig
ht
(kg)
0
1
5
0 3 6 9 12
8
7
6
4
3
2
Years
0 1 2 3 4 5
96
92
88
0
100
UKPDS 34. Lancet 1998:352:854–65. n=at baseline; Kahn et al (ADOPT). NEJM 2006;355(23):2427–43
Diabetes therapy:
Glucocentric VS.
• Pt with T2DM. Obesity complication
• Therapeutic target HgA1c
• Most common therapies >weight
• Based on UKPDS data
Adipocentric
• Pt with Obesity and comorb:T2DM
• Therapeutic target: BMI, abd. Cc
• Wt loss improves all CVRs (T2DM)
• Based on Look –AHEAD and
Stampede studies
Changes in Weight, Physical Fitness, Waist Circumference, and Glycated Hemoglobin Levels during 10 Years of Follow-up.
The Look AHEAD Research Group. N Engl J Med 2013;369:145-154
Mean Changes in Measures of Diabetes Control from Baseline to 3 Years.
Schauer PR et al. N Engl J Med 2014;370:2002-2013
Diabetes therapy:
Glucocentric VS.
• Pt with T2DM. Obesity complication
• Therapeutic target HgA1c
• Most common therapies >weight
• Based on UKPDS data
• 8 therapeutic classes to treat T2DM
• Acceptable Insurance coverage
Adipocentric
• Pt with Obesity and comorb:T2DM
• Therapeutic target: BMI, abd. Cc
• Wt loss improves all CVRs (T2DM)
• Based on Look –AHEAD and GBPS
Agent A1c Advantages Disadvantages Cost
SUs 1–2% Microvasc risk Hypo, wt gain, -cell exhaust
$
‘Glinides 1–1.5% PPG Hypo, wt gain, -cell exhaust, dose frequency
$ $ $
Biguanides 1–2% Wt loss, no hypo, CVD, ? malignancy
GI, lactic acidosis B12-deficiency
$
TZDs 1–1.5% No hypo; -cell preservTG HDL BP ? CVD (pio)
Wt gain, edema / HF Bone fxs, ? CVD (rosi)
$ $ $
-GIs 0.5–1% PPG, ? CVD; GI, dose frequency $ $
GLP-1 R agonists
1% Wt loss,? -cell preserv, ? CV benefits
GI; ? pancreatitis, injections
$ $ $
Amylino-mimetics
0.5% Wt loss, PPG GI, dose frequency, injections
$ $ $
DPP-4 inhibitors
0.6–0.8% No hypo Urticaria / Angioedema; ? pancreatitis
$ $ $
Bile acid sequestrants
0.5% No hypo; LDL-C GI; TGs $ $ $
D2 agonists 0.5% No hypo Nausea; dizziness $ $ $
T2DM: Therapeutic Landscape (Noninsulin) 2012
Inzucchi SE et al. Diabetes Care 2012;35:1364-1379.
Diabetes therapy:
Glucocentric VS.
• Pt with T2DM. Obesity complication
• Therapeutic target HgA1c
• Most common therapies >weight
• Based on UKPDS data
• 8 therapeutic classes to treat T2DM
• Acceptable Insurance coverage
Adipocentric
• Pt with Obesity and comorb:T2DM
• Therapeutic target: BMI, abd. Cc
• Wt loss improves all CVRs (T2DM)
• Based on Look –AHEAD and GBPS
• Five meds to treat obesity
• Very poor insurance coverage
Medications approved for chronic weight management and how they workhttp://www.accessdata.fda.gov/scripts/cder/drugsatfda/http://www.accessdata.fda.gov/scripts/cder/drugsatfda/.
ER: extended release; SR: sustained release. 5HT: serotonin. GABA: Gamma aminobutyric acid. GLP-1: Glucagon-like peptide 1.
Agent Action ApprovalScheduled
Drug
Orlistat
Xenical®
• Peripheral pancreatic lipase inhibitor - blocks ingested fat absorption
Approved 1997 • No
LorcaserinBelviq®
• 5-HT2C serotonin agonist• Little affinity for other serotonergic
receptors
Approved 2012 • YES
Phentermine/ Topiramate ER Qsymia™
• Sympathomimetic• Anticonvulsant (GABA receptor
modulator, carbonic anhydrase inhibitor, glutamate antagonist)
Approved2012 • YES
Naltrexone SR/ Bupropion SRContrave®
• Opioid receptor antagonist• Dopamine/noradrenaline reuptake
inhibitor
Approved2014 • No
Liraglutide 3.0 mgSaxenda®
• GLP-1 receptor agonist Approved2014 • No
Diabetes therapy:
Glucocentric VS..
• Pt with T2DM. Obesity complication
• Therapeutic target HgA1c
• Most common therapies >weight
• Based on UKPDS data
• 8 therapeutic classes to treat T2DM
• Acceptable Insurance coverage
• All algorithms are GLUCOCENTRIC
Adipocentric
• Pt with Obesity and comorb:T2DM
• Therapeutic target: BMI, abd. Cc
• Wt loss improves all CVRs (T2DM)
• Based on Look –AHEAD and
GBPS
• Five meds to treat obesity
• Very poor insurance coverage
Diabetes therapy:
Glucocentric VS.
• Pt with T2DM. Obesity complication
• Therapeutic target HgA1c
• Most common therapies >weight
• Based on UKPDS data
• 8 therapeutic classes to treat T2DM
• Acceptable Insurance coverage
• All algorithms are GLUCOCENTRIC
Adipocentric
• Pt with Obesity and comorb:T2DM
• Therapeutic target: BMI, abd. Cc
• Wt loss improves all CVRs (T2DM)
• Based on Look –AHEAD and GBPS
• Five meds to treat obesity
• Very poor insurance coverage
• Adipocentric algorithms are starting
Therapeutic algorithm for patientswith obesity and type 2 DM
Burguera B, Khawla F. Ali, Brito JP Antiobesity drugs in the management of type 2 diabetes:A shift in thinking? Clev Clin J Med. In press. July 2017
Changes in treatment:
• Slowly taper insulin
– Short acting first
• Stop Actos (or SU)
• Add metformin
• Add sGLT2 inh
• Consider also a GLP-1 analog
• An optimal approach to type 2 DM:
– control of glycemia and its associated comorbidities
• Obesity a key player
• Many of our first-line oral treatments for type 2 DM are
associated with weight gain
• Worsen control of glycemia insulin further exacerbating
therapy the weight gain
• It seems counterintuitive to treat a disease for which
obesity is one of the main risk factors, with
medications that promote weight gain
Approach to patient with obesity and Diabetes:
• Concentrating in the main problem: the obesity
• Treat the disease while we address the comorbidities
• Detailed medical history: Precipitating factors?
– physical activity, nutrition
– sleep, stress– depression–anxiety
• Look at the medications
• Identified colleagues who can help you:
– nutrition–exercise physiologist–sleep specialists
• Patient needs support, knowledge and tools
• Close follow-up.
• Consider shared medical appointments
• No hay excusa para no hacer acitividad fisica!
An intensive life-style program, offered to patients with severe obesity, who are not candidates or
not interested in undergoing bariatric surgery.
In the context of Shared Medical Appointments.
Team: Dietician, Nurse, Endocrinologist, Exercise Physiologist, Psychologist, and Surgeon
Endocrinology Institute and DDI (Bariatric Institute Institute).
Objective: To develop an optimal medical weight loss program to offer patients with BMI > 35
non-surgical candidates.
It is our goal to accomplish 5-10% weight after 12 months of intervention and weight loss
maintenance after 36 months.
T2DM: 25%
Program is now included in CCF Health Plan.
Cleveland Clinic Integrated Medical
Weight Management Program
We provide tools Accountability
1.- Nutrition: quality, quantity, portion sizes, drinks …
2.- Physical Activity: personalized exercise programs.
GOALS: short and midterm
3.- Appetite control: weight loss medications
4.- Sleep patterns. R/o OSA
5.- Stress. Depression. Anxiety
Bariatric surgery, if a medical approach is not successful
Emphasis on :
APPETITE
REGULATION
ADIPOSTAT: SET POINT
DIET PH ACTIVITY STRESS SLEEP
GI
signals
GI
FLORA
LIGHTFAT
signals
APPETITE
REGULATION
VITAMINS
MEDICATIONS
BARIATRIC SURGERYADIPOSTAT: SET POINT
Phases of Obesity Treatment
Phase I(Weight Loss)
3-6 months
Phase II(Weight-Loss Maintenance)
Indefinitely
When you stop treatment,
the disease comes back!
Weig
ht
PA compensates for the reduction in EE that occurs with weight loss and reduces the degree of caloric restriction required to stay in energy balance at a reduced body weightTo stay in energy balance at a reduced body weight, EI must decrease or EE must increase permanently from the pre-weight loss state
Energy Gap