TRATAMIENTO FARMACOLÓGICO DE

LA DIABETES
Diabetes mellitus tipo 1
Diabetes mellitus tipo 2
Diabetes mellitus tipo 2
Concepto de prediabetes
Sindrome metabólico
Sindrome metabólico: fisiopatología
Manejo del síndrome metabólico
Reducción del peso corporal
Orlistat: Eficacia
Orlistat: Eficacia
 MANEJO DE LA OBESIDAD: Nuevas drogas
antiobesidad

Lorcaserina

Facultad de Farmacia y Bioquímica - Universidad de Buenos Aires

 Lorcaserina

Lorcaserin: selective 5-HT2C receptor agonist

designed to promote weight loss
 5-HT2C receptor activation of proopiomelanocortin (POMC)
neurons results in α-MSH activation of melanocortin-4
receptors
 Serotonin receptor as a pharmacologic target for weight
loss was validated by fenfluramine
 Fenfluramine in combination with phentermine (Fen-Phen)
was highly efficacious for weight loss
 Safety concerns led to withdrawal: Fenfluramine activation
of 5-HT2B receptor was linked to cardiac valvular disease

Heisler LK, et al. Science. 2002;297:609-611.

 Behavioral Modification and Lorcaserin for
Obesity and Overweight Management (BLOOM)
Study Week
0
8 16 24 32 40 48 64 72 80 88 96 104

-2
Weight change (kg)

ITT/LOCF

-4 Per
Protocol

-6 ITT/LOCF

-8

-10
N = 344 N = 140 N = 308
PBO/PBO Lorc/PBO Lorc/Lorc
Lorcaserin (Lorc) vs placebo (PBO): P < .0001 at all timepoints
Lorc/Lorc vs Lorc/PBO: P < .0001 at all year 2 timepoints

Smith SR, et al. ADA 2009. Late-Breaking Abstract 96.

 Lorcaserin Did Not Increase the Rate
of FDA Valvulopathy
Treatment N n (%) P
Week 52
Lorcaserin 10 mg BID 1278 34 (2.66%) .70a
Placebo 1194 28 (2.35%)
Week 104
Lorcaserin/lorcaserin 500 13 (2.6%) .99a
Lorcaserin/placebo 258 5 (1.9%)
Placebo/placebo 627 17 (2.7%)
N = number of evaluable echo pairs; n = number (%) with FDA valvulopathy
aVs placebo with Fisher’s exact test

Smith SR, et al. ADA 2009. Late-Breaking Abstract 96.

 Lorcaserin: Adverse Events Reported by 5%
or More in Any Group in Year 1
N (%) Lorcaserin Placebo
(N = 1593) (N = 1584)
Headache 287 (18.0) 175 (11.0)
Dizziness 130 (8.2) 60 (3.8)
Nausea 119 (7.5) 85 (5.4)
Constipation 106 (6.7) 64 (4.0)
Fatigue 95 (6.0) 48 (3.0)
Dry mouth 83 (5.2) 37 (2.3)

Smith SR, et al. ADA 2009. Late-Breaking Abstract 96. 16

Potential Activities of Topiramate
Involved in Energy Balance
Activity Significance to Body Weight Loss
◼ Inhibits activity of glutamate at Reduces body weight (?)
AMPA/kainate receptors
◼ Inhibits activation of L-type Reduces body weight (?)
voltage-dependent Ca++ channels
◼ Inhibits carbonic anhydrase Reduces body weight (?)
(CA-II, CA-IV)
Reduces fat deposition
◼ Modulates lipoprotein lipase
activity and triglycerides
Reduces body weight
◼ Stimulates thermogenesis and
energy expenditure (some models) Reduces body weight, other
◼ Downregulation of corticotropin- effects on energy metabolism
releasing hormone, glucocorticoids
(GC), and GC receptors (depends
Effects on energy metabolism
on model)
◼ Other preliminary data
 Topiramate in Obesity: Percentage of Body
Weight Change From Baseline to Week 24
Weeks
0 2 4 6 8 10 12 14 16 18 20 22 24
0

-2
Placebo (n=48)
Weight Change (%)

-4 64 mg/d TPM (n=57)

-6 96 mg/d TPM (n=49)

192 mg/d TPM (n=50)

-8

384 mg/d TPM (n=44)

-10

P < .05 from week 4

TPM = topiramate
Bray G, et al. Obes Res. 2003;11:722-733.
 Proprietary Investigational Treatment
for Obesity
• Once-daily, oral, controlled-release formulation of low-
dose phentermine and topiramate
• Specifically designed to affect normal eating patterns
over 24 hours -- simultaneously addressing appetite,
satiety, and cravings Maximum
Approved
23 46 92 Doses

Topiramate
0 50 100 150 200 250 300 350 400 mg

Phentermine
0 3.75 5 7.5 10 15 20 25 30 mg
Low Mid Full (free base)

Press release. Sept 9, 2009. Available at: http://ir.vivus.com/releasedetail.cfm?ReleaseID=407933

Accessed April 27, 2010.
 EQUIP: Weight Loss Over Time
(Completer Population)
Placebo
-2.5%, 6 lb
Mean % Weight Loss

Low (23T, 3.75P)

-7.0%, 18 lb

Full (92T, 15P)

-14.7%, 37 lb

Data from patients who completed 56 weeks on treatment

Weeks
Patients Placebo Low Full
Completers (% of randomized) 241 (47%) 138 (57%)* 301 (59%)*
*Statistically greater number of patients completing study on combination drug vs placebo, P < .0001
Press release. Sept 9, 2009. Available at: http://ir.vivus.com/releasedetail.cfm?ReleaseID=420114
Accessed April 27, 2010.
 EQUIP: Significant Categoric Weight Loss With
Phentermine and Topiramate (Low and Full Dose)
% of Patients with:
Completers • ≥ 15% wt loss
Placebo 5%
15% Low 11%*
**P < .0001 vs placebo Full 43%**
*P = .026 vs placebo
• ≥ 10% wt loss
Weight Loss

Placebo 12%
10%
Low 27%**
Full 60%**
• ≥ 5% wt loss
5% Placebo 26%
Low 59%**
Full 84%**
0 10 20 30 40 50 60 70 80 90
% of Patients
Placebo Qnexa
LowLow Qnexa
FullFull
Press release. Sept 9, 2009. Available at: http://ir.vivus.com/releasedetail.cfm?ReleaseID=420114
Accessed April 27, 2010.
Efectos cardiovasculares de topiramato/fentermina
 EQUIP & CONQUER: TEAEs > 5%

EQUIP (N = 1264) CONQUER (N = 2485)

% of Patients
Placebo Low Full Placebo Mid Full
(N = 3749)
Dry mouth 3.7 6.7 17.0 2.4 13.5 20.8
Tingling 1.9 4.2 18.8 2.0 13.7 20.5
Constipation 6.8 7.9 14.1 5.9 15.1 17.4
Altered taste 1.0 1.3 8.4 1.1 7.4 10.4
Insomnia 4.9 5.0 7.8 4.7 5.8 10.3
Dizziness 4.1 2.9 5.7 3.1 7.2 10.0
Nausea 4.7 5.8 7.2 4.2 3.6 6.8
Blurred vision 3.1 6.3 4.5 3.6 4.0 6.0

Press release. Sept 9, 2009. Available at: http://ir.vivus.com/releasedetail.cfm?ReleaseID=420114

Accessed April 27, 2010.
Bupropion/Natrexona

Bupropion se cree que estimula la secreción de la

hormona anorexígena estimulante de los melanocitos
(αMSH) en células hipotalámicas productoras de pro-
opiomelanocortina, pero estimula de manera simultánea
la secreción de los productos de opioides endógenos de
proopiomelanocortina que podría inhibir la secreción de
αMSH, lo que limita la eficacia de bupropión.
La naltrexona bloquea este mecanismo autolimitante.
Bupropion/Natrexona
Bupropion/Natrexona
Bupropion/Natrexona: Efectos adversos
• Náuseas
• Estreñimiento
• Dolor de cabeza
• Vómitos
• Mareos
• Insomnio
• Sequedad en la boca
• Diarrea
Criterios diagnósticos 2018
Regulación de la glucemia
INSULINA
INSULINA
FARMACOCINÉTICA DE DIFERENTES INSULINAS
FARMACOCINÉTICA DE DIFERENTES INSULINAS
Ventaja de los nuevos análogos de la insulina
Ventaja de los nuevos análogos de la insulina
Ventaja de los nuevos análogos de la insulina
Ventaja de los nuevos análogos de la insulina
Insulinas inhaladas
INTERACCIONES MEDICAMENTOSAS
INTERACCIONES MEDICAMENTOSAS
EFECTOS ADVERSOS
HIPOGLUCEMIA
HIPOGLUCEMIA INADVERTIDA
HIPOGLUCEMIA
HIPOGLUCEMIA
Diabetes mellitus tipo 1: es posible su prevención o retraso?
Diabetes mellitus tipo 1: es posible su prevención o retraso?
TRATAMIENTO DIABETES MELLITUS TIPO II
TRATAMIENTO DIABETES MELLITUS TIPO II
Diabetes mellitus tipo 2
Diabetes mellitus tipo 2
Diabetes mellitus tipo 2
Eficacia antidiabética
METFORMINA
METFORMINA
METFORMINA
METFORMINA
SULFONILUREAS
SULFONILUREAS: Farmacocinética
SULFONILUREAS
SULFONILUREAS: Riesgo cardiovascular
SULFONILUREAS
MEGLITINIDAS
MEGLITINIDAS
Tiazolidinedionas
Tiazolidinedionas
ACARBOSA
ACARBOSA
ACARBOSA
INCRETINAS
INCRETINAS
Nuevos tratamientos:
Incretinomiméticos
Semaglutida: primer análogo GLP-1 oral
Nuevos tratamientos: Inhibición SGLT2
Nuevos tratamientos: Inhibición SGLT2
Nuevos tratamientos: Inhibición SGLT2
Nuevos tratamientos: Inhibición SGLT2
Nuevos tratamientos: Inhibición SGLT2
Nuevos tratamientos: Inhibición SGLT2
Beneficios cardiovasculares de agentes
antidiabéticos
Algoritmo en el tratamiento de la DM2
Algoritmo en el tratamiento de la DM2